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We evaluated the accuracy of estimating the cross-sectional area (CSA) at the third lumbar vertebra (L3) based on the CSA at the third cervical vertebra (C3) using computed tomographic images, and we identified the sources of error and bias using the evaluation of absolute reliability in 89 Japanese patients with oral squamous cell carcinoma.Skeletal muscle CSA was measured at the C3 and L3 on pretreatment computed tomographic images. We used the CSA at the C3 to estimate CSA at the L3 in an existing prediction formula. Correlation coefficients were used to evaluate the relative reliability of the estimate, and Bland-Altman analysis and minimum detectable change (MDC) were used to evaluate its absolute reliability.Estimated and actual CSAs at L3 were strongly correlated (r = 0.885, p 0.001). The mean difference between the estimated and actual CSAs was - 1.0887 cmThe estimation of CSA at the L3 from the existing prediction formula with the CSA at the C3 had no systematic biases, but it did have random errors. Random errors resulted from measurement errors and biological variation. Usefulness of the existing formula is limited by physical differences in populations.

The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma.Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/mHistopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients.These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.

Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed levels of H3K4me3/ H3K27ac and expression of a number of interferon-stimulated genes (ISGs), including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.

Ultrasound-guided inferior alveolar nerve block (UGIANB) is a mandibular analgesic procedure in which local anesthetic is injected into the pterygomandibular space (PMS). Several studies have reported the clinical efficacy of UGIANB for mandibular surgeries; however, its effective range has never been investigated. We performed a cadaveric study to investigate the success rate of UGIANB injections and to determine whether injected dye could stain the mandibular nerve (MN) trunk and its branches. We performed UGIANB on the bilateral faces of 4 Thiel-embalmed cadavers. A needle was advanced to the PMS under ultrasound guidance and 5 mL of dye was injected. The cadaver was dissected and inspected for the presence of dye in the PMS; the range of dye spread to any of the inferior alveolar nerve (IAN), lingual nerve (LN), buccal nerve (BN), mandibular nerve (MN), auriculotemporal nerve (ATN), or facial nerves; and for the presence of intravascular dye. We performed eight UGIANB procedures on four cadavers. Dye was observed in the PMS in 7/8 injections. Staining was observed in all IAN, LN, and BNs that could be identified at dissection. No MN or auriculotemporal nerves (ATNs) were stained in any injections. No intravascular dye was observed in any injections. UGIANB can administer anesthetic into the PMS with high accuracy. UGIANB injections reached the IAN, LN, and BNs, but did not reach the MN or ATNs located outside the PMS. The findings of this cadaveric study indicate that UGIANB can provide sufficient analgesia for mandibular surgeries.

Background/aim The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. Patients and methods We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. Results Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. Conclusion CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.

The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs.Publicly available single-cell RNA-sequencing (RNA-seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α-smooth muscle antigen (α-SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co-cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse-transcription PCR.Analysis of the RNA-seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12-positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α-SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co-cultured with OSCC cells.Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.

Intravascular papillary endothelial hyperplasia is an unusual benign lesion of vascular origin. A 56-year-old man presented with a mass in the right side of the lower lip. Before visiting our hospital, he had undergone 3 surgical procedures for recurrence of the mass in a short period of time. Clinical examination revealed a painless, soft, elastic, dark purple obscure mass measuring 17 × 11 mm in the right lower lip. Ultrasonography and magnetic resonance imaging suggested a hemangioma-like lesion. The possibility of malignant transformation could not be ruled out because of the clinical course up to that point, even though it had been histopathologically diagnosed as hemangioma. The lesion was surgically resected and the defect was reconstructed using a vermilion advancement flap combined with a V-Y advancement flap. The histopathological diagnosis was intravascular papillary endothelial hyperplasia. The patient has had no symptoms or any evidence of recurrence in the 4 years since the operation. His postoperative progress has been favorable both functionally and aesthetically.

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5‐year overall survival and disease‐specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC., Human leukocyte antigen class Ⅰ expression at the tumor invasive front could be a useful prognostic factor for oral squamous cell carcinoma.

The role of tumour-infiltrating CD45RoWe determined the density of tumour-infiltrating CD45RoFive-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45RoCD45Ro

Objective To clarify the relationship between mandibular ramus height and function of masticatory muscles in patients with hemifacial microsomia. Design Retrospective study of imaging and physiological data. Setting Images and physiological data were obtained from the records of Sapporo Medical University Hospital. Patients A total of 29 patients with hemifacial microsomia who showed Pruzansky grades I, II deformity. Main Outcome Measures Mandibular ramus height and masticatory muscle volume were evaluated with multi-detector row computed tomography. The electromyographic value was measured by the K7 Evaluation System. The hemifacial microsomia patients were classified into three groups based on the mandibular ramus height ratio of the affected and unaffected sides: group 0, > 1.00; group 1, 1.00 to 0.85; group 2, < 0.85. The Tukey-Kramer method and Games-Howell method were used to determine correlations between parameters. Results Decreased mandibular ramus height was significantly correlated with both reduced electromyographic values of the masseter muscle (P < .05) and the amount of mandibular lateral deviation at the time of maximum opening (P < .05) on the affected side. These differences were prominent in unilateral hemifacial microsomia patients classified as group 2. Conclusions Decreased mandibular ramus height may cause dysfunction of the masseter muscles but not the temporal muscle on the affected side in patients with hemifacial microsomia.

Objective Epithelial–mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis induced by hypoxia. Here, we examined whether phosphorylation of GSK3-β via phosphoinositide 3-kinase (PI3 K)/Akt signaling is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma (OSCC). Study Design Experiments were performed in OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was assessed by Matrigel invasion assays and wound healing assays. OSCC cell lines (HSC-2 and HSC-4) overexpressing hypoxia-inducible factor (HIF)-1α were established to examine the effects of HIF-1α on EMT-related factors. Immunohistochemical staining was performed to examine phosphorylation of GSK3-β in 33 cases of tongue squamous cell carcinoma. Results Under hypoxic conditions, OSCC cell lines exhibited HIF-1α expression and showed evidence of the EMT. In cells overexpressing HIF-1α, the levels of phospho-Akt and phospho-GSK3-β were increased, resulting in induction of the EMT. Inhibition of GSK3-β phosphorylation suppressed these effects. Moreover, the intensity of pGSK3-β staining was significantly increased with cN stage and cTNM stage in patients with tongue squamous cell carcinoma. Conclusions Our data showed that the hypoxia-induced EMT in OSCC was enhanced by GSK3-β phosphorylation, suggesting that GSK3-β may be important in the invasion and metastasis of OSCC.

Traumatic facial nerve paralysis is often caused by nerve damage in the temporal bone, such as that from temporal bone fractures, and very rarely by direct facial nerve injuries resulting from stings, cuts, bruises or other damage to areas outside of the temporal bone. We report a case of facial nerve paralysis due to pressure from a small bone fragment from a mandibular condylar fracture in which symptomatic improvement was achieved through surgical treatment. The patient was a 30-year-old woman who was injured during a fall. She visited our department after noticing symptoms the following morning that included malocclusion and abnormalities in the muscles of facial expression such as incomplete eye closure. On presentation, a left-side mandibular condylar fracture and severe left-side facial nerve paralysis were identified. As the likely cause of facial nerve paralysis was not a temporal bone fracture, cuts or bruises, but pressure from a small bone fragment, we performed open reduction and internal fixation (ORIF) surgery. In consideration of the surgical risk to nerves, ORIF surgery was performed using a transoral approach. Antecedent steroid therapy was begun just after hospitalization. Improvements were seen in both the malocclusion and facial nerve paralysis. Here we report a case of facial nerve paralysis due to compression from a small bone fragment from a condylar fracture that was treated with ORIF surgery through a transoral approach performed as decompression surgery with a favorable outcome.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. It accounts for 5% of all salivary gland tumors and 20% of salivary malignancies and has various clinical outcomes. Its prognosis is related to the tumor grade in the WHO classification of head and neck tumors. MEC is divided into high, intermediate and low grades. In general, low-grade MEC with cervical lymph node metastasis is rare, and primary MEC that occurs in a minor salivary gland with cervical lymph node metastasis is very rare. Low-grade lesions have quite different behavior from high-grade ones, leading to differences in the treatment course required for disease control. MEC is associated with recurring chromosomal translocation t(11;19)(q21;p13). CRTC1-MAML2 gene fusion was identified from the recurring translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript is detected frequently in MEC and is involved in the transformation of epithelial cells. Detection of the CRTC1-MAML2 fusion transcript is associated with a less advanced clinical stage and low-grade tumor histology. The presence of the transcript is associated with longer disease-free and overall survival periods. Here, we report a rare case of low-grade MEC with cervical lymph node metastasis. The findings for this patient show that the CRTC1-MAML2 fusion transcript may be specific to MEC, and associated with a distinct MEC subset that exhibits favorable clinicopathologic features.

To clarify the morphological characteristics of hemifacial microsomia (HFM) by quantitative analysis of cephalometric radiographs.Retrospective study of imaging data.Imaging data were obtained from the records of Sapporo Medical University Hospital.A total of 183 patients with HFM.We used linear and angular measurements and analyzed the middle face and lower face.The ratios of the affected side to the unaffected (A/U) side of the lateral distance of the mandibular condyle, the mandibular ramus height, and the length of the body of the mandible in the HFM group were significantly lower than in the control group. The inclination of the body of the mandible was significantly larger in the side with HFM than in the unaffected side, and the extent of the mandibular ramus was significantly lower than in the unaffected side. The A/U ratios of the extent of the angle of the mandible and the inclination of the body of the mandible in the HFM group were larger than in the control group. Moreover, the length and the inclination of the body of the mandible had significant correlations with the distance of the shift of the menton.It is suggested that improving the hypoplasia of the length of the body of the mandible and the extent of the angle of the mandible on the affected side will lead to more effective treatment of jaw deformity in patients with HFM.

Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues. We then validated their expression in 18 OSCC cell lines using qRT-PCR and identified 6 lncRNAs frequently overexpressed in OSCC. Among those, we found that knocking down DLEU1 (deleted in lymphocytic leukemia 1) strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion, and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC.

Background Facial asymmetry, which is often due to asymmetry of the mandible, is a naturally occurring phenomenon in patients with hemifacial microsomia (HFM). Only a few attempts have been made to develop specific quantitative diagnostic criteria for the mandibular asymmetry of HFM. This pilot study was designed to determine the soft-tissue and skeletal characteristics of patients perceived to have HFM and the factors affecting objective assessment of mandibular asymmetry. Methods Frontal facial photographs and frontal cephalograms of twelve patients who had HFM with mandibular asymmetry were analyzed. Landmarks and reference lines were determined on the basis of frontal photographs and cephalographic analysis. Linear measurements of the right and left sides were performed to assess the degree of asymmetry of the mandible. The differences between the affected side and the unaffected side were calculated and analyzed statistically. Results Significant differences were found for linear measurements of the gonion distance (GoD), full marginal distance (FMD), external marginal distance (EMD), and gonion-menton distance (Go-MeD) in the hard tissue and sFMD, sEMD, sGo-MeD in the soft tissue but not for the gonion distance in soft tissue (sGoD). The differences in sEMD and EMD were significantly correlated, and represented a valid factor affecting the mandibular asymmetry in soft and hard tissues. Conclusions The results of this study suggest that appropriate measurements affecting the outline of the mandible such as sEMD and EMD taken from frontal facial photographs and frontal cephalograms provide a useful, objective means of assessing mandibular asymmetry for patients with HFM.

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p

Purpose Morphologic evaluation of computed tomographic images is an important assessment tool before surgical removal of the lower third molar (LM3). The aim of this study was to ascertain whether the shape of the inferior alveolar canal (IAC) is a reliable predictor for inferior alveolar nerve (IAN) injury during M3 surgery. Materials and Methods This prospective study assessed samples with a high risk of IAN injury during M3 surgery based on orthopantomographic examination. The predictor variables were demographic factors (patient's age and gender), anatomic factors (angulation of the tooth), and radiographic factors (cortication status, buccolingual position, shape of the IAC, number of roots, and root shape). The outcome variable was IAN injury. The relation between predictor and outcome variables was analyzed using the Fisher exact test and a logistic regression model. Results One hundred sixty-nine LM3s (115 patients) were analyzed. IAN injury was observed in 12 of 115 patients and 13 of 169 LM3s (7.7%). All 13 cases with IAN injury exhibited absence of cortication. A dumb-bell–shaped IAC was considered a useful predictor for IAN injury (sensitivity, 69.2%; specificity, 84.6%). In cases with absence of cortication, logistic regression analysis indicated that a dumb-bell–shaped IAC was closely related to IAN injury ( P = .005). Conclusion The cortication status and shape of the IAC are reliable predictors for IAN injury at M3 surgery. Cases exhibiting absence of cortication and a dumb-bell–shaped IAC should be recognized as presenting a high risk of IAN injury at M3 surgery.

Object: Hypoxia occurs when oxygen tension drops below normal limits, and malignant tumors often experience hypoxia, which activates the expression of genes through oxygen-sensitive transcription factors, including the hypoxiainducible factor (HIF) and the nuclear factor-κB (NF-κB). NF-κB pathway represents an attractive therapeutic target in both cancer cells and ischemic cells, which involves immune response. To investigate the expression of NF-κB target genes in oral squamous cancer carcinoma (OSCC) under hypoxia, we performed cDNA plate array analyses of 23 NF-κB-regulated genes in different cell lines. Our aim was to clarify the functions of NF-κB in OSCC under hypoxia. Results: We conducted an NF-κB reporter assay to examine NF-κB activation under hypoxia. This luciferase-based reporter assay showed that hypoxia induced NF-κB activation after 24 h of hypoxia. We also found that vascular endothelial growth factor-C (VEGF-C) of NF-κB-regulated genes was upregulated in both cell lines under hypoxia. We then tested the influence of NF-κB/p65 knockdown on these cells and NF-κB/p65 knockdown inhibited the proliferation of OSCC cells by colony assay. Conclusion: Based on these findings, we postulate that one mechanism by which hypoxic OSCC cells may involve NF-κB-mediated upregulation. Our results also indicate that the knockdown of NF-κB/p65 subunit lead to growth inhibition during hypoxia in OSCC cells. These results suggest that knockdown of NF-κB/p65 subunit could be a potential therapeutic option for patients with OSCC.

Purpose To assess the clinical features of the inferior alveolar canal (IAC) using computed tomography (CT) and to analyze the significance of CT examination at third molar surgery. Materials and Methods A retrospective cohort study was performed involving 99 patients (145 teeth). The relationship between cortication status, buccolingual position, and shape of the IAC on the CT image and inferior alveolar nerve (IAN) injury after third molar surgery were statistically analyzed. Results The shape of the IAC was categorized into 3 groups: round/oval, teardrop, and dumbbell. IAN injury was observed in 7 of 145 cases (4.8%). All 7 cases exhibited absence of cortication; 3 were dumbbell shape and 4 were round/oval. According to logistic regression analysis of cases with absence of cortication, IAC shape was closely related to IAN injury. Conclusions These results suggest that assessment of the IAC shape and cortication status at third molar surgery may be clinically useful.

Background. Secondary cancers are severe complications in patients who have had allogeneic bone marrow transplantation for childhood leukemia. We describe here a case of squamous cell carcinoma (SCC) of the buccal mucosa in a young adult patient who had had allogeneic bone marrow transplantation for childhood acute leukemia. Methods and Results. The primary tumor was treated with interstitial brachytherapy, and lymph node metastasis was treated by supraomohyoid neck dissection. The patient had a history of acute lymphoblastic leukemia (ALL) at 11 years of age and had received an allogeneic bone marrow transplant from a female donor. Further investigation of the tissue specimens by fluorescent in situ hybridization (FISH) revealed that an XX chromosome pattern was dominant in the tumor region, and this suggested that donor-derived cells might affect carcinogenesis in the recipient. Conclusions. This case presents an incidence of secondary oral cancer associated with allogeneic bone marrow transplantation. © 2008 Wiley Periodicals, Inc. Head Neck, 2009

Solitary fibrous tumor (SFT) is a rare benign tumor that occurs mainly in the pleura; however, it can also arise in other extrapleural sites, including the oral cavity. In 2002, the World Health Organization classified SFT as a tumor of intermediate malignancy characterized by metastases to the lung, bone and, rarely, liver. We report a case of SFT in the left side of the buccal region. A 52-year-old woman visited our hospital in June 2005 because of a painless swelling on the left side of the buccal region. A CT scan and MRI showed awell-defined solid tumor in the left side of the buccal region. The tumor was surgically resected, and histopathological examination revealed a SFT. There has been no recurrence ofthe tumor for 18 months since the operation. We review the literature with regard to the clinicopathologic features of SFT.

Gene targeting using short interfering RNA (siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. For the application of siRNA technology to gene therapy, however, still more efficient transduction of siRNA into target cells is needed. In this study, we developed an adenoviral vector harboring a tandem-type siRNA expression unit, in which sense and antisense strands composing the siRNA duplex were separately transcribed by two human U6 promoters. Targeting survivin, an antiapoptotic molecule widely overexpressed in malignancies but not detected in terminally differentiated adult tissues, this type of adenoviral vector (Adv-siSurv) successfully exerted a gene knockdown effect and induced apoptosis in HeLa, U251, and MCF-7 cells. These cancer cells, once infected with Adv-siSurv, displayed remarkably attenuated growth potential, both in vitro and in vivo. Moreover, intratumoral injection of Adv-siSurv significantly suppressed tumor growth in a xenograft model using U251 glioma cells. This novel modality may be a promising tool for cancer therapy.

Objective: This study describes the patterns of the cervical metastatic lymph nodes of patients with oral carcinoma who received unilateral neck dissection and their correlation with the clinical course. Patients and Methods: Clinical examination of 72 patients with tongue, floor of the mouth, and mandibular gingival squamous cell carcinoma who had received unilateral neck dissection during an 11-year period between 1987 and 1997 was performed. Results: The survival rates of patients with 3 or more metastatic lymph nodes, and/or extracapsular nodes, and/or a metastatic level of III or IV were all lower than for patients with less than 3 metastatic lymph nodes (p = 0.002) and/or intracapsular nodes (p = 0.0118), and/or metastasis of level I or II (p = 0.0067). Multivariate analysis revealed that the number of metastatic lymph nodes was the factor of greatest influence in terms of prognosis. Conclusion: The prognosis for patients with 3 or more metastatic lymph nodes and/or extracapsular nodes are poor, so postoperative therapy such as radiotherapy should be considered for these patients.

Background Although naked plasmid injection is the safest and most convenient method for gene delivery, a major limitation of this approach is currently poor transgene expression. The CA promoter (chicken β-actin promoter with cytomegalovirus, CMV, enhancer) is one of the strongest transcriptional control modules found; however, it is uncertain whether a CA promoter-based vector is efficient enough for naked gene therapy in a cardiovascular context. Methods The β-galactosidase (LacZ) expression provided by CA promoter plasmid (pCAZ2) injection into the skeletal muscle or the heart of Lewis rats was compared with CMV promoter plasmid or adenoviral vector (AxCAZ3). The effect of Simian virus 40 of the replication origin (SV40ori) deletion from pCAZ2 on transgene expression was also evaluated. Results pCAZ2 showed the highest LacZ expression in both skeletal muscle and heart in comparison with the CMV promoter-based vector 5 days after naked plasmid injection. LacZ expression in the heart obtained using 20 µg of pCAZ2 was almost equivalent to that shown with AxCAZ3 at 6.0 × 109 optical particle units. The time course of transgene expression driven by CMV and CA promoters in the heart were similar, with the CA promoter providing significantly higher gene expression than the CMV promoter across all time points examined. SV40ori deletion from pCAZ2 did not affect transgene expression in either skeletal muscle or heart. Conclusions Transgene expression mediated by naked CA promoter-based plasmid injection was shown to be quite efficient in the heart. We propose that the CA promoter vector is suitable for myocardial gene therapy. Copyright © 2003 John Wiley & Sons, Ltd.

Interferon-gamma (IFN-gamma) induced cell death in five oral squamous cell carcinoma (SCC) lines. Cell death was specific to IFN-gamma treatment and did not occur with either IFN-alpha or TNF-alpha. IFN-gamma did not induce typical apoptotic phenotype in cells, such as morphological changes and DNA ladder formation. Caspase-3 was partially activated by IFN-gamma. Protein levels of molecular chaperones were examined in cells treated with IFN-gamma. Among these, levels of heat shock protein 27 (Hsp27) were specifically reduced upon IFN-gamma treatment of oral SCC cells. Recombinant clones overexpressing Hsp27 were more resistant to IFN-gamma-induced cell death than parent cells. Conversely, cells expressing a dominant-negative mutant of Hsp27, in which three serine residues (15, 78 and 82) were replaced by glycine, were hypersensitive to the effects of IFN-gamma and exhibited a typical apoptotic phenotype. Pretreatment of cells with IFN-gamma enhanced apoptotic cell death induced by cisplatin. Our data suggest that IFN-gamma suppresses Hsp27 expression in oral SCC cells and blocks the inhibitory effects of this molecular chaperone on apoptotic cell death. Moreover, IFN-gamma initiates the transition of oral SCC cells to the proapoptotic and/or aborted apoptotic state. Hsp27 plays a crucial role in the inhibition of apoptosis of oral SCC cells. Our findings highlight the importance of employing IFN-gamma in combination with certain anticancer drugs as treatments for oral cancer. We suggest that Hsp27 plays a significant role in the IFN-gamma-induced sensitization of oral SCC cells to anticancer drugs.

1978年から1997年の20年間に口腔悪性腫瘍切除後の再建術を施行した症例について臨床的検討を行った。テルダーミスやDuo-Activeなどの人工材料による再建術は34.0%, 舌弁や頬粘膜弁などの局所皮弁は18.9%, 胸鎖乳突筋皮弁は14.7%を占めた。遊離皮弁や大胸筋皮弁などの大規模な再建術症例は少なかった。胸鎖乳突筋皮弁施行例の原発巣は舌が9例, 口底が19例, 下顎歯肉が24例, 頬粘膜が3例, 口峡咽頭部が7例であり, それらのT分類はT1が2例, T2が20例, T3が11例, T4が29例であった。広頸筋皮弁施行例の原発巣は口底が4例, 下顎歯肉が1例, 頬粘膜が1例であり, それらのT分類はT1が1例, T2が3例, T3が1例, T4が1例であった。胸鎖乳突筋皮弁や広頸筋皮弁はマイクロサージェリーによる遊離皮弁に比して多くの手術時間を要せず, 肩甲舌骨筋上部郭清術や機能的郭清術をうまく適用すれば, これらの皮弁の適応が拡大するものと思われる。

舌 (10例) , 口底 (10例) , 下顎歯肉 (4例) 原発のN0の扁平上皮癌症例で片側の肩甲舌骨筋上部郭清術を行った24例について臨床的検討を行った。病理学的に転移リンパ節は8例 (33.3%) にみられたが, それらの臨床経過は良好であった。病理学的に転移リンパ節がみられなかった16例中1例が術後にみられた頸部転移により死亡しているが, 他の15例は再発, 転移なく生存している。3個の転移リンパ節が1例で, 1個が7例で認められた。転移リンパ節はlevel 1に6例で, level 2に2例でみられた。被膜外転移巣はlevel 1に2例でみられた。検索症例の大半では, 原発巣の病理組織学的悪性度は比較的高度であつた。今回の検索より, 原発巣の病理組織学的悪性度を考慮すれば, 肩甲舌骨筋上部郭清術は診断的効果のみならず治療的効果があがることが示唆された。

アデノウイルスベクターを用いた遺伝子治療は口腔癌を含むさまざまな悪性腫瘍に対して試みられている。口腔扁平上皮癌細胞株に対する野性型アデノウイルスベクターによる遺伝子導入効率は細胞株により差はあるものの低かった。これはアデノウイルスベクターの細胞吸着に関与する細胞表面の受容体であるコクサッキーアデノウイルスレセプター (CAR) の発現が低いためと考えられる。口腔扁平上皮癌細胞のCARmRNA発現量をABI PRISM 7700シーケンスディテクターを用いTaqMan PCRにより測定したところアデノウイルスで高い遺伝子導入効率を示す293細胞1として測定したところ, その発現量は0.12-0.54と低かった。そこでCARに非依存的なアデノウイルス遺伝子導入法を開発するために, TPC-COS法によりアデノウイルスファイバーノブのHIループにCDCRGDCFCインテグリン結合モチーフを導入したRGDファイバー変異型アデノウイルスベクターを作製し, 口腔癌細胞株での遺伝子導入効率を検討したところ, 野性型アデノウイルスベクターと比較し, 数倍から10倍の遺伝子導入効率の改善が得られた。以上の結果からRGDファイバー変異型アデノウイルスベクターはCAR発現量の少ない口腔扁平上皮癌に対する有用な遺伝子導入ベクターになりうることが示唆された。

We clinically examined 29 patients with squamous cell carcinoma of tongue, floor of the mouth, and maxillary gingiva who received unilateral functional neck dissection with preservation of the sternocleidmastoid muscle, internal jugular vein, and/or accessory nerve.The 5-year cumulative survival rate of all patients was 80.4%, that of 19 pN (+) patients was 68.6%, and that of 10 pN (-) patients was 100%. Pathologically, 4 metastatic lymph nodes (LNs) were found in 1 patient, 3 LNs in 3 patients, 2 LNs in 6 patients, and 1 LN in 9 patients. LNs were located in level 1 in 5 paitents, level 2 in 12, and level 4 in 2. Extranodular metastatic lesions were found in level 1 in 1 patient and in level 2 in 4. Among the patients with a poor prognosis, 2 LNs were found in 2 patients, 3 LNs in 1, and 4 LNs in 1, extranodular lesions were found in 2 patients, and LNs were located in level 2 in all patients.Our results suggest that functional neck dissection is indicated for patients who have single and movable nodular metastatic lymph node.

Background During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy. The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved. Methods Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK-8 assay. Analysis of the expression of HIF target genes in hypoxia-treated cells was performed using an HIF-regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT-PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry. Results The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein-1 (GLUT-1) was up-regulated in human squamous cell carcinoma of mouth (HSC-2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT-1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC-2, Ca9-22, and SAS (P = 0.025). Conclusion The results of this study suggest that knockdown of GLUT-1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC-2, Ca9-22, and SAS cells.