Souhei Furukawa

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer.

PURPOSE Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. METHODS AND MATERIALS The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. RESULTS Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.

Histopathologic and radiographic findings of the simple bone cyst

OBJECTIVE The purpose of this study is to examine the correlation between histopathologic and radiographic findings and to discuss the cause of the simple bone cyst. STUDY DESIGN Histopathologically, we classified 53 simple bone cysts into two types. Type A has a connective tissue membrane and type B has a partially thickened wall with dysplastic bone formation. Radiographically, we evaluated the following: margin, radiolucency, or radiopacity, relationship with tooth apices, bucco-lingual bone expansion, and displacement of the mandibular canal. RESULTS Bone expansion and radiopacity were closely related to histopathologic findings although there was no correlation between the histopathologic findings and radiographic margin, relationship with tooth apices, and displacement of mandibular canal. Local recurrence was more likely to be observed in patients diagnosed as having type B than type A lesions. CONCLUSIONS Type A and type B bone cysts may have different causes. Cysts determined radiographically to be radiopaque, those diagnosed as type B histopathologically, and cysts that have been treated surgically should all be followed by radiographic examinations.

Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes

We previously reported that CORS26 gene, isolated from C3H10T1/2 cells treated with transforming growth factor‐β1, was predominantly expressed in cartilage. Because the gene product is a kind of secretory protein produced by cartilage tissue, we named it “cartducin”. Cartducin shares a similar modular organization to adipocyte‐derived hormone, adiponectin. In this study, we investigated cartducin function during chondrogenesis and cartilage development. In situ hybridization analysis showed that cartducin transcripts were restricted to the proliferating chondrocytes in the growth plate cartilage. Whole‐mount in situ hybridization revealed that the first significant induction of cartducin expression occurred in the sclerotome, which contains a chondrogenic cell lineage between days 9.5 and 10.5 postcoitus (p.c.) during mouse embryogenesis. Chondrogenic differentiation by combined treatment with bone morphogenetic protein‐2 and insulin induced cartducin expression along with type II and IX collagen expression in chondrogenic progenitor N1511 cells. To elucidate the direct action of cartducin on the cells, recombinant cartducin protein was expressed in and purified from Escherichia coli. The recombinant cartducin potentially forms homo‐oligomers and promoted the proliferation of chondrogenic progenitor N1511 cells, and chondrocytic HCS‐2/8 cells in a dose‐dependent manner. On the other hand, cartducin did not affect the production of sulfated glycosaminoglycan (sGAG) in these cells. These findings indicate that cartducin is a novel growth factor and plays important roles in regulating both chondrogenesis and cartilage development by its direct stimulatory action on the proliferation of chondrogenic precursors and chondrocytes. J. Cell. Physiol. 206: 537–544, 2006.

Human Masticatory Muscle Volume and Zygomatico-mandibular Form in Adults with Mandibular Prognathism

Although several investigators have reported associations between masticatory muscles and skeletal craniofacial form, there is no agreement on the association. We tested the hypothesis that masticatory muscle volume correlates with the size and form of the adjacent local skeletal sites. For this purpose, we investigated the morphological association of the cross-sectional area and volume of temporal and masseter muscles with zygomatico-mandibular skeletal structures using computerized tomography (CT) in 25 male adults with mandibular prognathism. Muscle variables significantly correlated with widths of the bizygomatic arch and temporal fossa but not with the cranium width. Masseter volume significantly correlated with cross-sectional areas of the zygomatic arch and mandibular ramus. Masseter orientation was almost perpendicular to the zygomatic arch and mandibular antegonial region. The zygomatic arch angle significantly correlated with the antegonial angle. The results of the study suggest that the masticatory muscles exert influence on the adjacent local skeletal sites.

CTRP3/cartducin promotes proliferation and migration of endothelial cells

CTRP3/cartducin, a novel secretory protein, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. CTRP3/cartducin gene is transiently up-regulated in a balloon-injured rat carotid artery tissue. In this study, we report a new function of CTRP3/cartducin as a regulator of angiogenic processes. CTRP3/cartducin promoted proliferation and migration of mouse endothelial MSS31 cells in a dose-dependent manner. Further, stimulation of MSS31 by CTRP3/cartducin led to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). MAPK/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, and p38 MAPK inhibitor, SB203580, blocked the CTRP3/cartducin-induced cell proliferation, and migration was blocked by U0126, but not the SB203580. Taken together, these results suggest that CTRP3/cartducin may be involved as a novel angiogenic factor in the formation of neointima following angioplasty.

Spatial relationships between the mandibular central incisor and associated alveolar bone in adults with mandibular prognathism.

OBJECTIVE To examine if there was any correlation between the labio-lingual inclinations of the mandibular central incisor and the associated alveolar bone, and to investigate the labio-lingual position of the mandibular central incisor root apex in the associated cancellous bone in adults with untreated mandibular prognathism. MATERIALS AND METHODS High-resolution computed tomography images of the mandible were recorded in 20 adult patients with mandibular prognathism. The labio-lingual inclinations of a central incisor and its associated alveolar bone, the thickness of the associated cancellous bone, and the distance from the central incisor root apex to the inner contour of both the labial and lingual cortical plates were measured. Correlations and differences between the measured variables were tested for statistical significance. RESULTS The labio-lingual inclination of the central incisor significantly correlated with the labio-lingual inclination of the associated alveolar bone, the thickness of cancellous bone, and the distance from the central incisor root apex to the inner contour of the lingual cortical bone. The distance from the central incisor root apex to the inner contour of the labial cortical plate of bone was significantly smaller than that to the lingual cortical plate. CONCLUSIONS In adults with untreated mandibular prognathism, when the mandibular central incisor was more lingually inclined, the associated alveolar bone was also more lingually inclined and thinner. The mandibular central incisor root apex was closer to the inner contour of the labial cortical bone than to the lingual cortical bone.

Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal‐regulated kinase and phosphatidylinositol 3‐kinase/Akt pathways

Cartducin, a paralog of Acrp30/adiponectin, is a secretory protein produced by both chondrogenic precursors and proliferating chondrocytes, and belongs to a novel C1q family of proteins. We have recently shown that cartducin promotes the growth of both mesenchymal chondroprogenitor cells and chondrosarcoma‐derived chondrocytic cells in vitro. However, the cartducin‐signaling pathways responsible for the regulation of cell proliferation have not been documented. In this study, we examined whether cartducin exists in serum and further investigated the intracellular signaling pathways stimulated by cartducin in mesenchymal chondroprogenitor cells. Western blot analysis showed that, unlike Acrp30/adiponectin, cartducin was undetectable in mouse serum. Next, mesenchymal chondroprogenitor N1511 cells were stimulated with cartducin, and three major groups of mitogen‐activated protein kinase (MAPK) pathways and the phosphatidylinositol 3‐kinase (PI3K)/Akt signaling pathway were examined. Cartducin activated extracellular signal‐regulated kinase 1/2 (ERK1/2) and Akt, but not c‐jun N‐terminal kinase (JNK) nor p38 MAPK. The MEK1/2 inhibitor, U0126, blocked cartducin‐stimulated ERK1/2 phosphorylation and suppressed the DNA synthesis induced by cartducin in N1511 cells. The PI3K inhibitor, LY294002, blocked cartducin‐stimulated Akt phosphorylation and a decrease in cartducin‐induced DNA synthesis in N1511 cells was also observed. These data suggest that cartducin is a peripheral skeletal growth factor, and that the proliferation of mesenchymal chondroprogenitor cells stimulated by cartducin is associated with activations of the ERK1/2 and PI3K/Akt signaling pathways.

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer

PURPOSE To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.

LYMPH NODE METASTASIS OF EARLY ORAL TONGUE CANCER AFTER INTERSTITIAL RADIOTHERAPY

PURPOSE To examine the prognostic factors for lymph node metastasis after brachytherapy for early (T1-T2N0M0) oral tongue cancer. METHODS AND MATERIALS We reviewed the records of 571 patients (500 low dose rate and 71 high dose rate) treated at Osaka University Hospital between 1967 and 1999. RESULTS Patients with lymph node metastasis had tumor with an average diameter of 26 +/- 8 mm and a thickness of 9 +/- 5 mm; for patients without lymph node metastasis, the corresponding dimensions were 23 +/- 8 mm and 7.5 +/- 4 mm (p = 0.0004 and 0.001, respectively). After 5 years, the ulcerative (48%) and indurative/infiltrative (39%) types showed a higher ratio of nodal involvement than the exophytic (31%) and superficial (19%) types (p <0.0001). Multivariate analysis showed ulceration (p = 0.006) and a thickness of <or =6 mm (p = 0.04) to be statistically significant predisposing factors for lymph node metastasis. The lymph node control rate was 68% in 1967-1979, 71% in 1980-1990, and 66% in 1990-1999; the corresponding successful salvage rates for lymph node metastasis were 43%, 33%, and 58% (p = 0.04). CONCLUSION The appearance of the tumor, especially the presence or absence of ulceration and the diameter and thickness, are useful prognostic indicators for lymph node metastasis. Although the rates of lymph node metastasis did not change, the salvage outcome for recurrence after interstitial radiotherapy has recently improved.

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

PURPOSE Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. METHODS AND MATERIALS From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.