Kazuo Sano

Hypoxia-inducible factor 1 alpha in oral squamous cell carcinoma and its relation to prognosis

The aim of this study was to investigate the correlation between the expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and proliferative activity in tumor cells, lymph node metastasis, as well as prognosis in patients with oral squamous cell carcinoma (OSCC). Fifty-seven biopsy specimens of OSCC were investigated for the expression of HIF-1 alpha and proliferating cell nuclear antigen (PCNA) by immunohistochemistry. None of the patients had received any prior treatments. The percentage of HIF-1 alpha immunopositive area (PHIA) was calculated using computer-assisted image analysis for quantitative assessment of HIF-1 alpha expression. The PCNA labeling index (LI) was evaluated as a proliferation marker. We found that the mean PHIA in all stages was 12.1% in the poor prognosis patients, and it was 6.4% in the good prognosis patients. There was a significant difference of PHIA between poor prognosis and good prognosis patients (P=0.0065). Furthermore, the mean PHIA in the patients who had no metastatic lymph nodes was 7.5%, while it was 11.7% in the patients who had metastatic lymph nodes. There was also a significant difference of PHIA between patients who had no metastatic lymph nodes and those who had metastatic lymph nodes (P=0.0487). On the other hand, significant correlation between PHIA and PCNA LI was not observed. These results provide the clinical data indicating that HIF-1 alpha may play an important role in lymph node metastasis and prognosis in patients with OSCC.

Experimental study of combined hyperthermic and photodynamic therapy on carcinoma in the mouse

PURPOSE This study investigates the cytotoxic effect of photodynamic therapy using high-power laser irradiation on cancer cells. MATERIALS AND METHODS High- or low-power irradiation from a pulsed Nd:YAG dye laser with or without a photosensitizer was administered to an NR-S1 carcinoma in the mouse dorsum. RESULTS Photodynamic therapy with high-power laser irradiation yielded better results than conventional photodynamic therapy or hyperthermia with high-power laser irradiation. CONCLUSION Photodynamic therapy with high-power laser irradiation is more effective because it generates both a hyperthermic and a photodynamic effect.

Enhanced cell death in NR‐S1 tumor by photodynamic therapy: Possible involvement of Fas and Fas ligand system

To investigate the effect of photodynamic therapy (PDT) on cell death in malignant tumor tissue, the frequency of terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and the possible involvement of Fas and Fas ligand system were evaluated.

Effect of aging on the rat condylar fracture model evaluated by bromodeoxyuridine immunohistochemistry

PURPOSE The effect of aging on the recovery of cellular proliferative ability in the experimentally fractured rat condyle was studied by bromodeoxyuridine (BrdU) immunohistochemistry. MATERIALS AND METHODS The experimental animals (male Sprague-Dawley rats; n = 33, unilateral condylar fracture and sham operation) were divided into three age groups: 3, 6, and 36-weeks old. The cell proliferation was evaluated by the BrdU labeling index (LI) in the intermediate cell layer of the condyle at 1, 2, 4, 6, and 8 weeks after the fracture. RESULTS The cell kinetics of both condyles was affected by the temporomandibular joint dysfunction due to the unilateral condylar fracture. In all age groups, the fracture healed within 4 weeks. The LI of the nonfractured as well as fractured condyles decreased strikingly up to 2 weeks, and then only slightly increased at 4 weeks after the fracture. The LIs of the fractured condyles were lower than those of the control throughout the experiment regardless of age. Eight weeks after the fracture the percentage of recovery of the LI in the fractured condyle (LIs of fractured condyle in the fracture group/LIs of right condyle in the sham group) was 45.1% in 3-week-old-animals, 21.2% in 6-week-old-animals, and 16.1% in 36-week-old-animals. CONCLUSION This study shows that the recovery of cell proliferation in the fractured condyle depends on age.

BMP signaling is responsible for serum-induced Id2 expression.

Ids function as negative regulators of basic helix-loop-helix transcription factors and their expression is rapidly induced by serum stimulation in various cell types. In this study, we investigated the molecular basis of serum-induced expression of the mouse Id2 gene in NIH3T3 cells. A small-molecule inhibitor of bone morphogenetic protein (BMP) type I receptor kinases blocked the serum induction of Id2 mRNA. The chemical compound and several inhibitory proteins specific for BMP signaling suppressed the serum-induced activation of the luciferase construct with the mouse Id2 4.6-kb promoter region. Importantly, serum stimulation evoked rapid phosphorylation of Smad1/5/8 and significant activation of the reporter plasmid containing the recently identified BMP-responsive element (BRE) of the mouse Id2. Mutation analysis demonstrated that the binding sites for Smad proteins in the Id2 BRE were critical for serum response of the 4.6-kb whole construct. Gel shift and chromatin immunoprecipitation (ChIP) assays confirmed the serum-inducible binding of Smad1/5/8 and Smad4 to the Id2 BRE in vitro and in vivo. Finally, a knockdown experiment revealed the functional importance of Smad1 in the serum induction of Id2 expression. Thus, we concluded that BMP signaling is primarily responsible for the serum-induced Id2 expression. Our results also suggest that some of the cellular effects caused by serum are mediated through BMP signaling.

Pathological fracture of the mandible resulting from osteomyelitis successfully treated with only intermaxillary elastic guiding

Treatment of mandibular pathological fractures differs according to etiology. Closed reduction with intermaxillary fixation is usually performed when fractures occur as a result of osteomyelitis. Here is reported a case of pathological fracture of the mandible resulting from osteomyelitis that was successfully treated with intermaxillary elastics only.

Rapid Growing Myofibroma of the Gingiva: Report of a Case and Review of the Literature

PURPOSE Myofibroma is a rare benign tumor of myofibroblasts that rarely exhibits rapid enlargement and is misinterpreted as a malignant lesion. The aim of this study was to investigate its growth potential and to evaluate the usefulness of preoperative immunohistochemical study for an accurate diagnosis. MATERIALS AND METHODS A case of rapidly growing myofibroma of the lower gingiva was analyzed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography fused with computed tomography (PET/CT) and immunohistochemical study of Ki-67 and p53. The English-language literature from 1981 to 2012 also was reviewed. RESULTS An 18F-FDG PET/CT image displayed a high accumulation (maximum standardized uptake value, 14.1) in the lesion. A biopsy specimen showed mitotic activity of spindle-shaped cells, but atypia was not present. The MIB-1 labeling index was 10%, and the p53 test result was negative. The preoperative diagnosis of benign tumor of smooth muscle origin was made from the histopathologic and immunohistochemical features. In a review of 94 cases, tumors involved the mandible (33%), gingiva (23%), tongue (15%), cheek or buccal mucosa (12%), palate (8%), lip (4%), and other areas (5%). Nine cases (9.6%) were described as rapidly enlarging, and 8 cases (8.5%) were suspected of malignancy at initial diagnosis. The preoperative biopsy with immunohistochemical study established an accurate diagnosis in 83% of myofibromas, and no recurrences were reported in these patients. CONCLUSIONS Careful diagnosis is necessary because these lesions sometimes present clinical and radiologic features that resemble those of malignant tumors. Preoperative immunohistochemical analysis should be performed to avoid misdiagnosis or unnecessary aggressive therapy.

Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats

INTRODUCTION The aim of this study was to investigate the effects of systemically administered zoledronic acid (ZOL) on the progression of periapical lesions in estrogen-deficient rats. METHODS Female Wistar rats were divided into the following groups: SHAM-veh, sham surgery treated with vehicle (physiological saline); OVX-veh, ovariectomy treated with vehicle; SHAM-ZOL, sham surgery treated with ZOL; and OVX-ZOL, ovariectomy treated with ZOL. Vehicle or ZOL was administered intravenously once a week for 4 weeks. The pulp of the mandibular first molar of all rats was exposed to the oral environment to induce a periapical lesion, and the lesions were analyzed after 7 and 30 days. The mandibles were examined by micro-computed tomographic imaging and histopathologic, histometric, and immunohistochemical analyses. RESULTS Histopathologically, the OVX-veh group had more severe inflammation and bone loss and a larger number of cells that were positive for tartrate-resistant acid phosphatase compared with the SHAM-veh and OVX-ZOL groups; the SHAM-veh and OVX-ZOL groups were similar to each other. The SHAM-ZOL group had the lowest magnitude of these conditions. Tomographically, the OVX-veh group had greater bone loss than the other groups at both time points. The SHAM-veh, SHAM-ZOL, and OVX-ZOL groups had similar bone loss at both time points. In the sagittal section on day 30, the SHAM-ZOL group had lower bone loss compared with the SHAM-veh and OVX-ZOL groups. CONCLUSIONS The hypoestrogenic condition aggravates the progression of periapical lesions. ZOL therapy may help contain bone destruction of periapical lesions.

Diagnostic significance of FDG-PET and argyrophilic nucleolar organizer regions (AgNORs) in oral squamous cell carcinoma

Neoadjuvant chemoradiotherapy has played an important role in preserving organs and functions in patients with oral squamous cell carcinoma (SCC). To determine whether further operation after chemoradiotherapy is necessary, accurate evaluation of residual tumour cells after treatment is essential. We investigated the usefulness of regional fluorodeoxyglucose (FDG) uptake in combination with histochemical expression of AgNORs obtained from pretreatment biopsy specimens to assess residual tumours after intraarterial chemoradiotherapy. Standardized uptake value (SUV: pretreatment, pre-SUV; post-treatment, post-SUV) was calculated to determine the changes of FDG uptake in the tumour before and after chemoradiotherapy. Four out of 20 patients with oral SCCs showed residual tumour cells after treatment. Tumours with higher post-SUVs (> or =4.0) and higher AgNORs scores (> or =5.0) had significantly higher incidences of residual viable tumour cells after chemoradiotherapy (P=0.001). The results suggest that the combination of FDG-PET with AgNORs score is an excellent index for determining the optimal management of each patient following neoadjuvant chemoradiotherapy.

The free deltoid flap: microscopic anatomy studies and clinical application to oral cavity reconstruction.

&NA; The deltoid free flap is a fasciocutaneous flap that should be thin, hairless, of an adequate size, and capable of sensory reinnervation. Because of its excellent colormatching and texture‐matching characteristics, it has recently been widely used for the reconstruction of softtissue defects during oral and maxillofacial surgery. Furthermore, a characteristic of oral and maxillofacial soft‐tissue defects is that they are not large; therefore, flap size will be small, allowing the donor site to be directly closed. Because of natural variation in parts of the anatomy, there has sometimes been great difficulty in clinical application. The authors decided to study this by performing anatomical studies of the deltoid region on 21 cadavers. The result indicates that the pedicle of the deltoid free flap penetrates the “quadrangular space” in 90 percent of cases but passes and does not penetrate the quadrangular space in the remaining cases. The authors also confirmed that the skin has a vascular network comprising five layers and, furthermore, that the vascular network of the deep fascia is dense. The authors also report six cases of its clinical use complicated by anatomic variation and local infection in which the deltoid flap showed a completely successful outcome. (Plast. Reconstr. Surg. 112: 404, 2003.)