Noriko Kawai

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer

We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of the histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription in oral cancer cell lines were analyzed by RT-PCR. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, and even SAS and KB cells expressed high levels of hTERT. Moreover, cotreatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation/deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, and depended on the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute to FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved transcription factors other than c-myc, in addition to inhibition of histone deacetylation.

A radiographic study on resorption of tooth root associated with malignant tumors

AbstractRoot resorption is a very important finding in the radiographic diagnosis of the oral and maxillofacial region. However, there are few reports about root resorption related to malignant tumors. It is a commonly accepted theory that a malignant tumor does not cause root resorption because its invasion is too rapid. However, we have encountered many unexpected cases of root resorption associated with malignant tumors. In this study, we investigated the frequency and shape of root resorption in malignant tumors and considered the relation between tumor extension and root resorption. The subjects were 72 patients with pathologically diagnosed malignant tumors. Radiography showed that the roots of their teeth were in contact or involved with the tumors. We observed the radiographs and classified the findings into 2 types as follows:(1)resorption of alveolar bone (site of tumor invasion): 1. alveolar-margin type 2. root-apex type.(2)resorption of tooth root: 1. spike type 2. knife-edge type. The root resorption rate for all cases was 43% (31/72). (There were 19 squamous cell carcinomas, 2 adenoid cystic carcinomas, 3 malignant lymphomas, 2 metastatic tumors, 1 poorly differentiated carcinoma, 3 undifferentiated carcinomas and 1 fibrosarcoma.) Root resorption rate of alveolar-margin-type tumors was 37% (19/51), and that of the root-apex-type tumors was 57% (12/21). All alveolar-margin-type tumors showed spike-type root resorption, and all root-apex-type tumors were of the knife-edge type except 1 case. Our study suggested that root resorption associated with malignant tumors is not rare and that the shape of root resorption may be related to the site of tumor invasion. In the case of root resorption with resorption of alveolar bone, it is important to take malignant tumors into consideration as well as other diseases.

Functional MRI Study of Cerebral Cortical Activation during Volitional Swallowing

ObjectivesTo investigate the somatotopic distribution and lateralization of motor and sensory cortical activity during swallowing in healthy adult human subjects using functional MR imaging.MethodsNine healthy right-handed adult volunteers (6 men, 3 women; ages 22–38) were examined. Their cortical activities were evoked by having them swallow, five times, asmall bolus of water (3 ml) supplied through a plastic catheter. As a positive control, the subjects performed five repetitions of right-handed grasping tasks. Blood oxygenation level-dependent images were obtained using a 1.5 Tesla MR system (Magnetom Vision, Siemens Germany; TR/TE=0.96/0.66, FA=90°). T1 weighted anatomical images were obtained for the same slices in each subject.ResultsCerebral activity was observed most notably in the primary motor cortex and primary somatosensory cortex, followed by the premotor cortex, anterior cingulate cortex, frontal operculum, and insula. The hand-grasping task activated relatively superior parts of the primary motor and somatosensory cortices. The swallowing task, on the other hand, activated the inferior parts of the pre- and postcentral gyri. The hand-grasping activation of motor and sensory cortices was localized absolutely on the contralateral side, whereas swallowing activated the motor cortex either bilaterally or unilaterally. Swallowing activated the sensory cortex almost always bilaterally.ConclusionsThis study suggested that fMRI could be used to identify the specific areas of cortical activation caused by various tasks, and to differentiate the locations of cortical activation between tasks.