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H Tanzawa

Publications and source records attributed to H Tanzawa.

At least 19 recordsLinked to original sources
PubMed2006

Ubiquitous mitochondrial creatine kinase downregulated in oral squamous cell carcinoma.

In this study, we performed two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionisation time of fly mass spectrometry to identify the protein(s) associated with the development of oral squamous cell carcinomas (OSCCs) by comparing patterns of OSCC-derived cell lines with normal oral keratinocytes (NOKs), and found that downregulation of ubiquitous mitochondrial creatine kinase (CKMT1) could be a good candidate. Decreased levels of CKMT1 mRNA and protein were detected in all OSCC-derived cell lines examined (n=9) when compared to those in primary normal oral keratinocytes. Although no sequence variation in the coding region of the CKMT1 gene with the exception of a nonsense mutation in exon 8 was identified in these cell lines, we found a frequent hypermethylation in the CpG island region. CKMT1 expression was restored by experimental demethylation. In addition, when we transfected CKMT1 into the cell lines, they showed an apoptotic phenotype but no invasiveness. In clinical samples, high frequencies of CKMT1 downregulation were detected by immunohistochemistry (19 of 52 (37%)) and quantitative real-time RT-PCR (21 of 50 (42%)). Furthermore, the CKMT1 expression status was significantly correlated with tumour differentiation (P<0.0001). These results suggest that the CKMT1 gene is frequently inactivated during oral carcinogenesis and that an epigenetic mechanism may regulate loss of expression, which may lead to block apoptosis.

Apoptosis↗
PubMed2006

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis.

Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase-polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.

Aged↗
PubMed2006

Association between commensal bacteria and opportunistic pathogens in the dental plaque of elderly individuals.

Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.

Aged↗
PubMed2005

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma.

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis.

Adult↗
PubMed2005

Aberrant expression of RAB1A in human tongue cancer.

This study was designed to identify specific gene expression changes in tongue squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared from normal oral tissues, primary oral cancers, and oral cancer cell lines. The genes identified by our microarray system were further analysed at the mRNA or protein expression level in a series of clinical samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and imuunohositochemistry. The microarray analysis identified a total of 16 genes that were significantly upregulated in common among four TSCC specimens. Consistent with the results of the microarray, increased mRNA levels of selected genes with known molecular functions were found in the four TSCCs. Among genes identified, Rab1a, a member of the Ras oncogene family, was further analysed for its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in premalignant lesions (93%). Thus, our results suggest that rapid characterisation of the target gene(s) for TSCCs can be accomplished using our in-house cDNA microarray analysis combined with the qRT-PCR and immunohistochemistry, and that the Rab1A is a potential biomarker of tongue carcinogenesis.

Aged↗
PubMed2003

Differential distribution of glycosaminoglycans in human cementifying fibroma and fibro-osseous lesions.

OBJECTIVE: Differential diagnosis of cementifying fibroma, ossifying fibroma and fibrous dysplasia by histological evaluation is often difficult. The aim of this study was to examine the immunoreactivities for keratan sulfate (KS) and chondroitin-4-sulfate (C4S) glycosaminoglycans of the histological samples obtained from mandibles of patients with these diseases. MATERIALS AND METHODS: The samples were collected from three patients with cementifying fibroma, two with ossifying fibroma and three with fibrous dysplasia and were subjected to immunohistochemical analyses. RESULTS: The results demonstrated that a significant immunoreactivity for KS was found in lacunae housing cells in the cementum-particles of cementifying fibromas, while both ossifying fibromas and fibrous dysplasias showed no significant immunoreactivity for KS. For C4S, while the former showed little immunoreactivity, the latter two cases exhibited intensive immunostaining in the pre- and poorly mineralized matrices. CONCLUSIONS: These results suggest that cementifying fibromas could be distinguished from these fibro-osseous tumors by using immunohistochemical analysis for KS and C4S.

Adolescent↗
PubMed2003

Expression of an inhibitor of apoptosis, survivin, in oral carcinogenesis.

A novel inhibitor of apoptosis, survivin, plays a role in oncogenesis. To determine the potential involvement of survivin in oral carcinogenesis, we investigated the distribution of survivin protein expression in oral squamous cell carcinomas (OSCCs) and oral pre-malignant lesions. The mRNA expression level and methylation status of the gene also were evaluated in OSCCs and OSCC-derived cell lines. In immunohistochemistry, 58% of tumors and 37% of pre-malignant lesions examined were positive for survivin, while no immunoreaction was observed in corresponding normal tissues. The reverse-transcription/polymerase chain-reaction revealed similar changes in survivin gene expression levels. Furthermore, of the 9 normal oral tissues with no survivin gene expression, 4 showed methylation of the gene, while no methylation was detected in the corresponding tumorous tissues. The results suggest that survivin plays an important role during oral carcinogenesis, and that the gene expression may be regulated by an epigenetic mechanism.

Antigens, Neoplasm↗
PubMed2002

Oral bacteria influenced by the functional status of the elderly people and the type and quality of facilities for the bedridden.

AIMS: To analyse the relationship between oral bacteria and the health and functional status of the elderly. METHODS AND RESULTS: The bacteria species in the oral cavity of the elderly were examined. It was found that the bedridden subjects staying at two hospitals for long-term (HOBR) showed significantly lower detection rates of commensal bacteria species and significantly higher detection rates of Pseudomonas aeruginosa, of methicillin-resistant Staphylococcus aureus (MRSA) and of coagulase(-) Staph. aureus than those living independently (the independent). In addition, the detection rate of Haemophilus parainfluenzae in NUBR was discovered to be higher than that found in the independent. In HOBR, the detection rate of Ps. aeruginosa was significantly higher among in-patients who required continual care than those in need of partial care, while the detection rate of MRSA was significantly higher among in-patients with low serum albumin than those with normal serum albumin. CONCLUSIONS: Oral bacteria examination analysis proved that the risks of infection of some pathogenic bacteria species were correlated with functional status, physical function and nutritional state. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study suggests that the oral bacteria, especially pathogenic bacteria were influenced by the functional status of the elderly and the type and quality of the facilities for the bedridden, physical function and nutritional state.

Activities of Daily Living↗
PubMed2001

Analysis of the ANA gene as a candidate for the chromosome 21q oral cancer susceptibility locus.

Loss of heterozygosity (LOH) on the long arm of chromosome 21 (21q) is observed in several human malignancies. We identified novel tumour suppressor loci on this region in primary oral squamous cell carcinomas (OSCCs). To further determine the role of 21q deletions in oral cavity tumorigenesis, 63 OSCCs were examined for LOH at 21q using 7 microsatellite markers. LOH was observed in 32 of 63 cases (50.8%) that were informative for at least one of the loci analysed. Two distinct deleted regions were identified at chromosomal region 21q11.1. The possible involvement of ANA (abundant in neuroepithelium area), a candidate tumour suppressor gene (TSG) located on 21q11.2--21.1, was also evaluated for 20 OSCCs and 9 OSCC-derived cell lines. 60% of tumours (12/20) and 88.9% (8/9 cell lines) showed absent or reduced mRNA gene expression; only one OSCC case had a nucleotide substitution in the ANA gene. Interestingly, the frequency of the suppressed ANA mRNA expression was greater in stage IV tumours than in earlier stages. In addition, re-expression of the ANA gene mRNA was induced in 4 cell lines after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. These findings demonstrate that there may be at least 2 distinct TSGs on 21q11.1; loss of ANA gene expression could be involved in the progression of human OSCC; and aberrant methylation of the ANA gene promoter may participate in the transcriptional silencing of the gene in oral cancer cells.

Azacitidine↗
PubMed2001

Analysis of a role for p16/CDKN2 expression and methylation patterns in human oral squamous cell carcinoma.

The p16/CDKN2 (cyclin dependent kinase number 2) gene is known to be one of the negative regulators of the cell cycle. Aberrant 5'CpG island methylation is one of the most important mechanisms of p16/CDKN2 gene promoter region alteration. We studied 8 oral squamous cell carcinoma cell lines and 25 primary tumor tissues for the p16/CDKN2 gene and its expression by PCR-SSCP, MSP, RT-PCR, and immunohistochemical methods to determine the mechanism and the potential biological significance of p16/CDKN2 gene inactivation. In primary tumors, no p16/CDKN2 gene mutations were found by PCR-SSCP. However, hypermethylation of the CpG sites of p16/CDKN2 gene was observed in 48% (12/25) cases of primary tumors and in 50% (4/8) of cell lines. To verify the p16 mRNA expression, we employed RT-PCR and observed decreased or lacked p16 mRNA in 44% (11/25) of primary tumor tissues. In addition, hypermethylation was observed in 6 of the above 11 cases (55%). An immunohistochemistry assay was also performed with the primary tumor tissues, and a semi-quantitative method was used to evaluate the staining intensity of p16 protein. We observed 52% (13/25) negative nuclear staining. When we compared these results with clinicopathological stages, there was no statistical significance. These findings suggest that hypermethylation of p16/CDKN2 promoter region may be associated with p16/CDKN2 gene alteration.

Aged↗
PubMed2001

Alterations of collagen matrix in weight-bearing bones during skeletal unloading.

Skeletal unloading induces loss of bone mineral density in weight-bearing bones. The objectives of this study were to characterize the post-translational modifications of collagen of weight-bearing bones subjected to hindlimb unloading for 8 weeks. In unloaded bones, tibiae and femurs, while the overall amino acid composition was essentially identical in the unloaded and control tibiae and femurs, the collagen cross-link profile showed significant differences. Two major reducible cross-links (analyzed as dihydroxylysinonorleucine and hydroxylysinonorleucine) were increased in the unloaded bones. In addition, the ratios of the former to the latter as well as pyridinoline to deoxypyridinoline were significantly decreased in the unloaded bones indicating a difference in the extent of lysine hydroxylation at the cross-linking sites between these two groups. These results indicate that upon skeletal unloading the relative pool of newly synthesized collagen is increased and it is post-translationally altered. The alteration could be associated with impaired osteoblastic differentiation induced by skeletal unloading that results in a mineralization defect.

Amino Acids↗
PubMed2001

A detailed deletion map of chromosome 20 in human oral squamous cell carcinoma.

Loss of heterozygosity (LOH) on the long arm of chromosome 20 (20q) has been detected in several human cancers. However, little is known about LOH on chromosome 20 in oral squamous cell carcinoma (OSCC). To determine which loci of chromosome 20 were involved in OSCC tumorigenesis, 41 cases of OSCC were examined for LOH state on chromosome 20 at 17 microsatellite loci by PCR-LOH assay. LOH occurred in 41.5% of tumors in at least one locus. Among the 17 loci, D20S48 on 20p11.2 and RPN2 on 20q12-13.1 exhibited higher frequencies of LOH, 27.6% and 31.4%, respectively. The LOH incidence was significantly higher in tumors in which the primary site was on gingiva compared with other oral sites (p=0.012). Our results indicate that allelic deletions on 20q12-13.1 and 20p11.2 may play roles in OSCC carcinogenesis, and suggest that allelic deletions on 20q might have some relation with the primary site of OSCC.

Carcinoma, Squamous Cell↗
PubMed2000

Allelic loss in human intrahepatic cholangiocarcinoma: correlation between chromosome 8p22 and tumor progression.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver in Japan. Despite progress in operative techniques and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progression of ICC. We screened allelic losses at 6 loci, including that of novel tumor-suppressor gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parameters. As a result, 61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258, relatively frequent LOH was detected (17.6%) compared with other loci on chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass-forming + periductal infiltrating type were frequently detected by LOH at D8S258 compared to cases of the mass-forming or intraductal growth type. In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.

Aged↗
PubMed2000

Low levels of NPM gene expression in UV-sensitive human cell lines.

Nucleophosmin (NPM) is a major nuclear matrix protein associated with neoplastic growth in various cell types. We recently suggested that expression of the NPM gene is involved in an increased resistance to UV irradiation in human cells against the cell-killing effects of UV (mainly 254nm wavelength far-ultraviolet ray) [Y. Higuchi, K. Kita, H. Nakanishi, X-L. Wang, S. Sugaya, H. Tanzawa, H. Yamamori, K. Sugita, A. Yamaura, N. Suzuki, Biochem. Biophys. Res. Commun. 248 (1998) 597-602]. In the present study, expression levels of the NPM gene were examined in human cell lines with a high sensitivity to UV cell-killing. Cockayne syndrome patient-derived cell lines, CSAI and CSBI, and the Xeroderma pigmentosum patient-derived cell line, XP2OS(SV), XP13KY, XP3KA, XP6BE(SV), XP101OS and XP3BR(SV), have been investigated for their NPM mRNA expression with Northern blotting analysis. All of these UV-sensitive cells demonstrated lower expression levels compared with those of normal fibroblast cells, FF, or an UV-resistant cell line, UH(r)-10; quite a lower level of expression in XP205(SV) cells after UV irradiation in contrast to a distinguishable increase in the expression in UV(r)- cells. These results confirmed an intimate correlation between degree of UV sensitivity and expression levels of the NPM gene in human cells.

Cell Survival↗
PubMed2000

Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control.

The ability to metabolise carcinogens or pro-carcinogens, repair DNA damage, and control cell signalling and the cell cycle are fundamental to homeostasis. Oral squamous cell carcinoma (oral cancer) and many squamous cell carcinomas of the head and neck (SCCHN) may, under appropriate exposure to mutagens, arise if these mechanisms are defective. SCCHN arise as a consequence of multiple molecular events induced by the effects of various carcinogens from habits such as tobacco use, influenced by environmental factors, possibly viruses in some instances, against a background of heritable resistance or susceptibility. Consequent genetic damage affects many chromosomes and genes, and it is the accumulation of these changes that appears to lead to carcinoma in some instances, sometimes via a clinically evident pre-malignant, or potentially malignant, lesion. Although lifestyle factors play a prominent role in aetiology, some patients appear susceptible because of an inherited trait in their ability or inability to metabolise carcinogens or pro-carcinogens, possibly along with an impaired ability to repair the DNA damage. This is the first of a series of three papers reviewing the advances in the understanding of this area of research since our last review [Scully C, Field JK. Genetic aberrations in squamous cell carcinoma of the head and neck (SCCHN), with reference to oral carcinoma (Review). Int J Oncol 1977;10:5-21] and discusses mainly oral carcinoma in the context of SCCHN.

Alcohol Drinking↗
PubMed2000

Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations.

Carcinogenesis is the result of a series of genetic mutations resulting in unregulated growth of a clone of cells and the development of malignant lesion that is largely monoclonal though, with the evolution of further genetic changes, there develops a degree of heterogeneity in the tumour. DNA technology, especially allelic imbalance (loss of heterozygosity) studies have identified chromosomal changes in oral carcinoma and head and neck squamous cell carcinoma (SCCHN), suggestive of the involvement of tumour suppressor genes (TSGs), particularly in chromosomes 3, 9, 11 and 17. The regions most commonly identified have included 3p, especially 3p14.2 (FHIT); 3p24, and 3p21.3, where the TSGs involved are as yet unidentified; 9p21 where p16 (INK4A/MTS-1] is the main target TSG; and 17p13 where p53 is the major target TSG. Over-expression of oncogenes, genes mainly involved in cell signalling, especially those on chromosome 11 (PRAD-1 in particular) and 17 (H-ras) and mutations in DNA repair genes, have also been implicated in the carcinogenesis of SCCHN.

Carcinoma, Squamous Cell↗
PubMed2000

Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing.

STUDY OBJECTIVES: To examine dose-dependent effects of mandibular advancement on collapsibility of the passive pharynx and sleep-disordered breathing (SDB). DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: Thirty-seven adult patients with SDB. INTERVENTIONS: Oral appliances with 2-, 4-, and 6-mm advancement of the mandible. MEASUREMENTS AND RESULTS: Overnight oximetry was performed with and without oral appliances. Each 2-mm mandibular advancement coincided with approximately 20% improvement in number and severity of nocturnal desaturations. Percentages of patients producing a > 50% improvement rate of the number of desaturations were 25%, 48%, and 65% with use of oral appliances with 2-, 4-, and 6-mm mandibular advancement, respectively. Static pharyngeal mechanics were evaluated in six completely paralyzed patients with SDB under general anesthesia with and without the oral appliances. Advancement of mandibular position was found to produce dose-dependent closing pressure reduction of all pharyngeal segments. Normalization of nocturnal oxygenation was associated with negative closing pressure, especially at the velopharynx. CONCLUSIONS: We conclude that improvement of both nocturnal oxygenation and pharyngeal collapsibility significantly depends on the mandibular position.

Adult↗