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Biomedical subjects

S Shintani

Publications and source records attributed to S Shintani.

158 records · Page 9Linked to original sources
PubMedDate not supplied

Cariogenicity of the probiotic bacterium Lactobacillus salivarius in rats.

Probiotic bacteria such as lactobacilli and bifidobacteria are considered to be non-pathogenic and non-toxigenic on the basis of long years of safe usage. However, some species of lactobacilli are thought to be associated with the development of dental caries. The purpose of the present study was to examine the cariogenicity of the probiotic bacterium Lactobacillus salivarius in rats. Rats were divided into six groups, and infected with L. salivarius LS1952R and/or Streptococcus mutans MT8148R. L. salivarius LS1952R became established in the oral cavity of rats and induced significant level of dental caries even when infected for only 5 days from 18 to 22 days of age. In addition, the caries scores of rats superinfected with both Streptococcus mutans MT8148R and L. salivarius LS1952R from 18 days of age were significantly higher than those infected with either L. salivarius LS1952R or S. mutans MT8148R alone. Since strain LS1952R can adhere to saliva-coated hydroxyapatites, it is concluded that L. salivarius strain LS1952R possesses an inherent cariogenic activity following adherence to the tooth surface.

Analysis of Variance↗
PubMedDate not supplied

p53 and MDM2 expression in oral squamous cell carcinoma.

The p53 tumor suppressor gene is the most commonly mutated gene in human cancer and is a frequent abnormality in oral squamous cell carcinoma and its precancerous lesions. MDM2 (murine double minute-2), a new proto-oncogene, may be associated with p53 gene products and may negatively affect the transcriptional activating function of p53. The purpose of this study was to investigate the incidence of MDM2 and its relationship to the expression of p53 in oral squamous cell carcinoma and precancerous lesions. Overexpression of p53 and MDM2 proteins was detected in 52 and 40% of oral squamous cell carcinomas, respectively. p53 gene mutation, absent in normal oral epithelium was observed in 31% of the carcinoma cases. Our finding suggested that MDM2 protein may be an alternative mechanism causing p53 protein dysfunction in oral squamous cell carcinoma.

Base Sequence↗
PubMedDate not supplied

The relationship of shape of tumor invasion to depth of invasion and cervical lymph node metastasis in squamous cell carcinoma of the tongue.

Several investigators have suggested that there is a strong correlation between tumor depth and lymph node involvement in tongue carcinoma. The purpose of this study was to investigate the relationship between the shape of tumor, tumor depth, and lymph node metastasis in tongue carcinoma. Fifty-four patients with T1 abd T2 tongue carcinomas who underwent surgical treatment were included in this study. Tumors were divided into four categories according to their shape of invasion: superficial, exophytic, endophytic, and a combination of endophytic and exophytic. Forty cases of endophytic and combination types were divided into two groups according to the shape of invasion: (1) reductive bottom of invasion (n = 17) and (2) expansive bottom of invasion (n = 23). Tumors with a reductive bottom of invasion showed a variety of tumor depths and had low lymph node involvement (4/17, 23.5%). However, tumors with an expansive bottom of invasion showed deeper invasion and a high incidence of lymph node metastasis (16/23, 69.6%). These results suggested that the macroscopic shape of invasion is a feature that may provide important information about the prognosis of the primary tumor especially in relation to cervical lymph node involvement.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Expression of Cu,Zn-SOD, Mn-SOD and GST-pi in oral cancer treated with preoperative radiation therapy.

Radical scavengers play an important role in cancer cells defending themselves against free radicals which occur with irradiation. SOD (Cu,Zn, Mn-) and GST-pi are radical scavengers with an effect on radiation therapy. We investigated the correlation between radiation effects and expression of Cu,Zn-, Mn-SOD and GST-pi in 34 cases of oral cancer, treated with preoperative radiation therapy. In this study, 22 cases out of 34 were classified as effective and 12 cases as non-effective. Expression of Cu,Zn, Mn-SOD and GST-pi were observed in 13 (38.2%), 10 (29.4%) and 20 (58.8%) cases, respectively. Regarding the value of radiation sensitivity from expression of these proteins in the biopsy samples, no significant correlation was found between those expressions and histological effectiveness of preoperative radiation therapy. But interestingly, in 11 out of 12 of the non-effective cases, strong staining of Cu, Zn-SOD and GST-pi were shown at the residual cancer cells after preoperative radiation therapy. These results suggested that the expression of SOD (Cu,Zn-, and Mn-) and GST-pi may be not useful markers for predicting the effects of radiation therapy. However, Cu, Zn-SOD and GST-pi were increased by irradiation and may play an important role in radiation resistance and cancer cell regeneration after radiation therapy.

Adult↗
PubMedDate not supplied

The influence of blood arterial oxygen condition on the tumor response to preoperative radiation therapy in oral cancer patients.

The relationship between clinicopathological factors and response of radiation therapy in oral squamous cell carcinoma has been studied. It has been suggested that factors such as tumor site, extent and tumor differentiation determine the response to radiation therapy. It is known that oxygenation is related to the therapeutic effects of radiation therapy. However, there are few reports on the relationship between oxygen condition and the response to radiation therapy. The present study was carried out to assess whether any clinicopathological factors, including an evaluation of the oxygen condition can be used to predict the effects of preoperative radiation therapy in oral squamous cell carcinomas. Forty-seven patients with oral cancer treated with external radiation therapy preoperatively were evaluated. There were no significant differences in response to the radiation with respect to age, sex, tumor site, stage, macroscopic shape of tumors, and the histological factors. The hemoglobin (Hb) and arterial oxygen content (CaO(2)) levels of favorable cases (Hb: 14.4 g/dl, CaO(2) 19.1 ml/dl) were significantly higher than those of unfavorable cases (Hb: 11.0 g/dl, CaO(2): 16.1 ml/dl). These findings suggest that oxygen conditions of oral cancer patients predict tumor response to preoperative radiation therapy.

Aged↗
PubMedDate not supplied

Infrequent alternations of RB pathway (Rb-p16INK4A-cyclinD1) in adenoid cystic carcinoma of salivary glands.

Retinoblastoma (Rb) tumor suppressor genes' products and of the proteins regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1, play important roles in the regulation of the cell cycle. Rb gene inactivation, reflected by the absence of Rb protein expression, has been reported in oral squamous cell carcinomas. p16INK4A is frequently deleted, methylated, or mutated, and cyclin D1 gene amplification in many malignancies including oral squamous cell carcinomas (SCC). These findings suggested that Rb pathway of G1 arrest are the most commonly affected genes in Oral SCC. However, alternation of Rb pathway in salivary gland tumors was not clear. In this study, the expressions of Rb, p16INK4A, and cyclin D1 alternations were analyzed by immunohistochemical assay in 5 specimens of normal salivary glands and twenty-two cases of adenoid cystic carcinomas (ACC). Proliferating cell nuclear antigen (PCNA) labelling index (P.I.) was used for the evaluation of cell proliferation. Rb was consistently expressed in normal salivary glands and ACC. Loss of p16INK4A expression was observed in three cases (13.6%) of ACC. And overexpression of cyclin D1 was observed in four cases (18.2%). The three p16INK4A absent cases were the tumors with predominantly solid pattern and those cases were overexpressed cyclin D1. The cell proliferation activities of p16INK4A absent tumors (P.I. = 24.2 +/- 2.1%) were significantly higher than those of p16INK4A present tumors (P.I. = 10.4 +/- 3.5%) (P < 0.05). Cyclin D1 expression was also related to cell proliferation (P.I. of cyclin D1 negative cases vs. cyclin D1 positive: 10.1 +/- 3.0% vs. 22.6 +/- 3.4%) (P < 0.05). These findings suggested, however, alternations of Rb pathway were infrequent events in ACC of salivary glands and inactivation of p16INK4A, cyclin D1 overexpression may be related to the high cell proliferating activity of ACC.

Adult↗
PubMedDate not supplied

Comparisons of the pharmacokinetics and the leukopenia and thrombocytopenia grade after administration of irinotecan and 5-fluorouracil in combination to rats.

BACKGROUND: Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). Preliminary data on this combination therapy in humans demonstrated no drug interactions between CPT-11 (or its metabolite, SN-38) and 5-FU however, because there is so little information on the combination, the possibility for an interaction still exists. MATERIAL AND METHODS: CPT-11 and 5-FU were injected intravenously into rats and the pharmacokinetics of CPT-11 and SN-38 and alternations in blood cell count were investigated. RESULTS: In the group of rats administered 5-FU prior to CPT-11, the area under the concentration-time curve (AUC) of CPT-11 was approximately eight-fold larger compared with the group administered CPT-11 prior to 5-FU. On the other hand, the grade of leukocytopenia or thrombocytopenia was not significantly different among the two groups. CONCLUSION: In rats, the conversion of CPT-11 into SN-38 is possibly delayed by prior administration of 5-FU.

Animals↗
PubMedDate not supplied

Stereoselective metabolism of carvedilol in the rat. Use of enantiomerically radiolabeled pseudoracemates.

14C-Labeled R(+)- and S(-)-carvedilol enantiomers were prepared by direct resolution of 14C-labeled racemic carvedilol on a chiral HPLC column. Two enantiomerically radiolabeled carvedilol pseudoracemates, 14C-labeled R(+)/unlabeled S(-)-carvedilol and 14C-labeled S(-)/unlabeled R(+)-carvedilol, were reconstituted and administered orally and iv to separate groups of bile duct-cannulated rats to determine the biliary excretion of carvedilol enantiomers and the stereochemical composition of metabolites excreted into the bile. The respective biliary excretions of the radioactivity derived from the radiolabeled R(+)- and S(-)-enantiomers accounted for 41.4 +/- 0.9 and 41.5 +/- 1.9% of the oral racemic dose, and 43.7 +/- 2.4 and 40.0 +/- 0.9% of the iv dose. Oral administration of these pseudoracemates produced no enantiomeric difference in the biliary excretion of the radioactivity derived from the enantiomers, whereas iv administration did result in an enantiomeric difference: the biliary excretion rate of the radioactivity derived from R(+)-enantiomer was higher than that from S(-)-enantiomer. After administration by the two routes, two carbazole ring-hydroxylated glucuronides, 1-hydroxycarvedilol O-glucuronide (1-OHCG) and 8-hydroxycarvedilol O-glucuronide (8-OHCG), were detected as the major metabolites in the bile. The S/R enantiomer ratios of 1-OHCG were 0.59 for oral dosing and 0.43 for iv dosing, suggesting that the formation of 1-OHCG is selective for R(+)-enantiomer, while the S/R ratios of 8-OHCG showed values of 3.29 and 2.63 for oral and iv administrations, respectively, favoring S(-)-enantiomer. Since corresponding hydroxylated metabolites are rapidly biotransformed to glucuronides that are excreted predominantly in the bile, the stereoselectivity of these glucuronides presumably reflects that of carbazole ring hydroxylation.

Administration, Oral↗
PubMedDate not supplied

Cell proliferation and tumor angiogenesis in oral squamous cell carcinoma.

Cell proliferation and vascularization play an important role in the metabolic functions of normal and malignant tissues. Tumor cell proliferation and density of microvessels (DM) in 33 specimens of oral squamous cell carcinoma (SCC) were assessed by immunohistochemical staining of proliferating nuclear cell antigen (PCNA) and JC/70A, respectively. Their staining patterns were compared to the clinicopathologic findings. The PCNA labeling index (LI) showed significantly higher values in advanced carcinomas (T3 and T4) (mean, 20.19 +/- 12.79) than in early carcinomas (T1 and T2) (mean, 9.58 +/- 4.01; P < 0.01). The DM (mean, 105.92 +/- 22.65) and PCNA LI (mean, 25.69 +/- 13.32) of tumors with lymph node metastasis were significantly higher than in tumors without nodal involvement (DM, mean, 72.6 +/- 24.30; P < 0.01) (PCNA LI, mean, 10.25 +/- 3.99; P < 0.001). Marginal DM values were significantly correlated and directly proportional to the mode of tumor invasion. Evaluation of PCNA and DM at the periphery of the tumor may help to identify oral SCC that have higher malignant potential.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Regional lymph node involvement affects the incidence of distant metastasis in tongue squamous cell carcinomas.

Locoregional control of tongue cancer has improved. However, the incidence of distant metastases is rising, and a significant increase in long-term survival has failed to materialize. In our study, twenty-two (9.9%) of the 223 patients presented distant metastases. The incidence of distant metastases was significantly related to the tumor size and the regional lymph node involvement. Large (T4) lesions showed a higher risk for having distant metastases than T1-3 lesions (p < 0.01). The group with pathologic presence of disease in the neck lymph nodes had more than three times as many distant metastases as did those with pathologic absence (8.1% versus 26.8%). Moreover, 8 out of 13 (61.5%) patients with more than four pathological positive lymph node had distant metastasis. Tongue carcinoma patients with T4 lesion and four or more positive nodes had the highest risk of distant metastases and these patients may benefit from adjuvant systemic treatment.

Adult↗
PubMedDate not supplied

Overexpression of p53 is an early event in the tumorigenesis of oral squamous cell carcinomas.

The purpose of this study was to determine the timing of p53 overexpression during the development of oral squamous cell carcinomas. Immunohistochemical analysis of p53 expression was performed on 107 cases of oral squamous cell carcinoma, 37 cases of leukoplakia, and 10 cases of cancer-free patient's normal oral mucosa samples. 43 of the 107 (40.2%) oral squamous cell carcinomas showed p53 overexpression. There was no relationship between p53-overexpression and clinicopathological factors, such as size of tumors, lymph node metastasis, hostological differentiation and prognosis. Overexpression of p53 was not detected in 10 normal mucosa. Seven out of 37 (18.7%) samples of leukoplakia and 15 out of 43 (34.8%) samples of noncancerous epithelium adjacent to the p53-positive carcinomas showed p53 overexpression, the results demonstrate that p53 protein may have an important role in the early stages of oral tumorigenesis.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Expression of c-erbB family gene products in adenoid cystic carcinoma of salivary glands: an immunohistochemical study.

The tyrosine kinase receptor family, including the epidermal growth factor receptor (EGF-R), c-erbB2 and, more recently, the c-erbB3, has been recognized as being of particular importance in many human malignancies. This study was undertaken to define the role of c-erb B2 and c-erbB3 in adenoid cystic carcinomas (A.C.C.) of the salivary glands. Sixteen cases of A.C.C. were studied immunohistochemically, using antibodies against each erbB gene family product. EGF-R was not detected in any of these samples but c-erbB2 and c-erbB3 gene products (ERBB2and ERBB3) were demonstrated in all A.C.C. sections with some degree of straining. Tubular and cribriform patterns overexpressed particularly large amounts of ERBB2 and ERBB3. Strong staining was mainly demonstrated in tumor cells of the invasive area. These results suggested that overexpression of ERBB2 and ERBB3 is related to tumor differentiation and invasion in adenoid cystic carcinomas.

Adult↗
PubMedDate not supplied

Paradoxical hyperfixation of hexamethylpropyleneamine oxime in cerebral infarction.

We describe four patients with cerebral infarction and 99mTc-hexamethylpropyleneamine oxime (HMPAO) hyperfixation in distributions corresponding to the infarctions seen at CT and/or MR imaging. Increased HMPAO extraction due to hyperpermeability across the blood-brain barrier and increased retention due to reduced back diffusion of the tracer probably accounted for the increased fractional fixation in infarcts seen in our patients.

Aged↗