Tomonao Aikawa

Hedgehog Proteins Stimulate Chondrogenic Cell Differentiation and Cartilage Formation

Sonic hedgehog (Shh) and Indian hedgehog (Ihh) are important regulators of skeletogenesis, but their roles in this complex multistep process are not fully understood. Recent studies have suggested that the proteins participate in the differentiation of chondrogenic precursor cells into chondrocytes. In the present study, we have tested this possibility more directly. We found that implantation of dermal fibroblasts expressing hedgehog proteins into nude mice induces ectopic cartilage and bone formation. Immunohistological and reverse‐transcription polymerase chain reaction (RT‐PCR) analyses revealed that the ectopic tissues derived largely if not exclusively from host cells. We found also that treatment of clonal prechondrogenic RMD‐1 and ATDC5 cells in culture with Ihh or recombinant amino half of Shh (recombinant N‐terminal portion of Shh [rShh‐N]) induced their differentiation into chondrocytes, as revealed by cytoarchitectural changes, Alcian blue staining and proteoglycan synthesis. Induction of RMD‐1 cell differentiation by Ihh or rShh‐N was synergistically enhanced by cotreatment with bone morphogenetic protein 2 (BMP‐2) but was blocked by cotreatment with fibroblast growth factor 2 (FGF‐2). Our findings indicate that hedgehog proteins have the ability to promote differentiation of chondrogenic precursor cells and that their action in this process can be influenced and modified by synergistic or antagonist cofactors.

Decision analysis and treatment threshold in a management for the N0 neck of the oral cavity carcinoma

The optimal method of management of clinical N0 neck in squamous cell carcinoma of the oral cavity remains controversial. We used decision analysis to determine the current optimal strategy in comparison with observation of the neck and elective neck dissection. A total of 165 previously untreated patients with N0 classification were investigated. Probabilities of each recurrence were calculated and probabilities of being cured in each event were substituted with the 5-year overall survival calculation with Kaplan-Meier method. A sensitivity analysis was performed to determine the optimal threshold for treatment of the N0 neck. The threshold of N0 neck was calculated using the formula with putting the three probabilities of being cured. In this study the threshold was estimated at 44.4%. N0 neck of squamous cell carcinoma of the oral cavity should be observed if the probability of occult metastasis is less than 44.4%. Proper calculation of three probabilities of being cured in each institution will make a decision of the optimal method of clinical N0 neck by using the threshold formula.

Tumor Thickness and Paralingual Distance of Coronal MR Imaging Predicts Cervical Node Metastases in Oral Tongue Carcinoma

BACKGROUND AND PURPOSE: The presence of cervical lymph node metastases is an important prognostic factor for oral tongue cancer. The accurate preoperative assessment is essential for treatment. Several studies have suggested that histologic tumor thickness is related to the metastases. The aim of this study was to determine whether MR images of oral tongue tumor have the potential to predict cervical lymph node metastases. MATERIALS AND METHODS: A total of 43 patients with squamous cell carcinoma of the oral tongue were investigated. Tumor thickness, sublingual distance between tumor and sublingual space, and paralingual distance between tumor and paralingual space, as determined from coronal MR imaging, were preoperatively estimated. Logistic regression analysis was used to identify independent predictors of lymph node metastases. RESULTS: Univariate logistic regression analysis showed that T classification, N classification, and 3 measured MR imaging distances (millimeters) were significantly associated with lymph node metastases. Multivariate logistic regression analysis showed that tumor thickness (odds ratio, 1.34; 95% confidence interval [CI], 1.11–1.63; P < .005) and paralingual distance (odds ratio, 0.53; 95% CI, 0.35–0.82; P < .005) were significant predictors for lymph node metastases. The probability of metastases was estimated with these models. The preoperative decision (20% probability) as to whether to perform neck dissection could be based on tumor thickness of >9.7 mm and paralingual distance of <5.2 mm. CONCLUSION: MR images provide satisfactory accuracy for the preoperative estimation of the tumor thickness and the paralingual distance, which are valuable for predicting cervical lymph node metastases.

Intraductal carcinoma of the tongue: Report of a case

A case of intraductal carcinoma arising from a minor salivary gland of the tongue is reported. The relevant literature is discussed.

Differential expression of aquaporin 5 and aquaporin 3 in squamous cell carcinoma and adenoid cystic carcinoma

Aquaporins (AQPs) are a membrane protein family involved in the selective transport of water across cell membranes. Recent studies have reported the expression of AQP5 in several tumor types such as gastric, pulmonary, ovarian, pancreatic and colorectal cancer. We have previously reported the expression on tumor cells and the important role of AQP3 on cell growth in tongue cancer. However, little is known about the expression and precise role of AQP5 on squamous cell carcinoma (SCC) of the tongue. We investigated the expression of AQP5 and AQP3 in human oral SCC and adenoid cystic carcinoma (ACC). Overexpression of both AQP5 and AQP3 were immunohistochemically observed on tumor cells in SCC, whereas ACC cells were faintly stained with those antibodies against AQPs. Treatment with pan-AQP inhibitor or specific AQP5-siRNA showed inhibition of cell growth in SCC cell lines via the inhibition of integrins and the mitogen-activated protein kinase pathway. AQPs play important roles in cell growth in SCC rather than ACC.

Induction chemotherapy is Associated with an increase in the incidence of locoregional recurrence in patients with carcinoma of the oral cavity

This study was conducted to determine long term survival rates and the pattern of failure in patients with carcinoma of the oral cavity treated with induction chemotherapy or preoperative radiotherapy followed by surgery.

Monocarboxylate Transporter 10 Functions as a Thyroid Hormone Transporter in Chondrocytes

Thyroid hormone is essential for normal proliferation and differentiation of chondrocytes. Thus, untreated congenital hypothyroidism is marked by severe short stature. The monocarboxylate transporter 8 (MCT8) is a highly specific transporter for thyroid hormone. The hallmarks of Allan-Herndon-Dudley syndrome, caused by MCT8 mutations, are severe psychomotor retardation and elevated T(3) levels. However, growth is mostly normal. We therefore hypothesized that growth plate chondrocytes use transporters other than MCT8 for thyroid hormone uptake. Extensive analysis of thyroid hormone transporter mRNA expression in mouse chondrogenic ATDC5 cells revealed that monocarboxylate transporter 10 (Mct10) was most abundantly expressed among the transporters known to be highly specific for thyroid hormone, namely Mct8, Mct10, and organic anion transporter 1c1. Expression levels of Mct10 mRNA diminished with chondrocyte differentiation in these cells. Accordingly, Mct10 mRNA was expressed most abundantly in the growth plate resting zone chondrocytes in vivo. Small interfering RNA-mediated knockdown of Mct10 mRNA in ATDC5 cells decreased [(125)I]T(3) uptake up to 44% compared with negative control (P < 0.05). Moreover, silencing Mct10 mRNA expression abolished the known effects of T(3), i.e. suppression of proliferation and enhancement of differentiation, in ATDC5 cells. These results suggest that Mct10 functions as a thyroid hormone transporter in chondrocytes and can explain at least in part why Allan-Herndon-Dudley syndrome patients do not exhibit significant growth impairment.

Nasolabial cyst in a patient with cleft lip and palate

Nasolabial cysts are rare non-odontogenic cysts that occur beneath the ala nasi, and debate about their complicated, unique pathogenesis continues. It is widely accepted that these lesions originate from the anlage of the nasolacrimal duct; however, some still think that nasolabial cysts arise from fissural cysts. The authors report a patient with a nasolabial cyst who also had a unilateral cleft lip and palate. This unusual finding may indicate a different origin for nasolabial cysts than what has been accepted in the past.

Rotational movement of the anterior maxillary segment by hybrid distractor in patients with cleft lip and palate.

OBJECTIVE Maxillary anterior segmental distraction osteogenesis (MASDO) is an effective surgical orthodontic treatment for the retruded maxilla in cleft lip and palate because of its benefit of the conservation of velopharyngeal function. Some reports showed MASDO using various devices, but they do not allow the rotational movement of the distracted anterior segment. In this article, we showed MASDO using hybrid distracters (DynaForm System: Stryker Osteosymthesis, Leibinger Micro Implants, Kalamazoo, MI), which allow the advance of the distracted segment with rotational movement. METHOD The hybrid distractor with 4 metal arms is secured beyond both alveolar osteotomy lines on each side. These 2 distractors permit rotational movement of the segment by controlling the amount of advancement on each side. RESULTS For 6 patients with cleft lip and palate, MASDO using hybrid distractors was performed and the anterior segment moved at planned positions without any complications except lip discomfort, which disappeared after removal of the distractor. CONCLUSION MASDO, using an institutionally diagnosed hybrid distractor can successfully achieve the necessary rotational movements of the anterior maxillary segment owing to its design, which incorporates some mechanical flexibility.

Role of endothelin receptor signalling in squamous cell carcinoma

Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ETA and ETB are highly expressed in lung and skin tumor tissues. In contrast, there are few reports on endothelin signalling in the proliferation of head and neck cancer. We found that both ETA and ETB endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ETA and ETB were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ETA selective antagonist (BQ123) or an ETB selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ETA or ETB. Furthermore, inhibition of the mitogen-activated protein (MAP) kinase pathway by the treatments with ET receptor antagonists and siRNA was also observed. These results indicate that endothelin signalling may, in part, play important roles in cell growth in SCCs through the MAP kinase pathway.