C1q/TNF-related protein 3 expression and effects on adipocyte differentiation of 3T3-L1 cells.

Adipose tissue-derived adipokines influence a number of organs critical for energy homeostasis and metabolism. One of the most extensively studied adipokines is adiponectin, which exerts anti-diabetic, anti-inflammatory, and anti-atherogenic functions on various cell types. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 reduces hepatic triglyceride levels in diet-induced obese (DIO) mice. However, the physiological role of CTRP3 in adipocytes is largely unknown. In the course of our investigation of expression profiles of CTRPs during adipocyte differentiation, we found that CTRP3 expression pattern is different from that previously reported. Therefore, we examined the effect of CTRP3 on adipogenesis using 3T3-L1 cells. The expression level of CTRP3 was markedly decreased during the differentiation of 3T3-L1 cells. Recombinant CTRP3 (rCTRP3) treatment significantly reduced intracellular lipid content and decreased expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, and fatty acid binding protein 4 (FABP4) in 3T3-L1 cells. Furthermore, rCTRP3 induced the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and Akt in differentiated 3T3-L1 adipocytes. These results suggest that CTRP3 may negatively regulate lipid metabolism during adipocyte differentiation.

Preventing Complications from High-Dose Rate Brachytherapy when Treating Mobile Tongue Cancer via the Application of a Modular Lead-Lined Spacer.

PURPOSE: To point out the advantages and drawbacks of high-dose rate brachytherapy in the treatment of mobile tongue cancer and indicate the clinical importance of modular lead-lined spacers when applying this technique to patients. METHODS: First, all basic steps to construct the modular spacer are shown. Second, we simulate and evaluate the dose rate reduction for a wide range of spacer configurations. RESULTS: With increasing distance to the source absorbed doses dropped considerably. Significantly more shielding was obtained when lead was added to the spacer and this effect was most pronounced on shorter (i.e. more clinically relevant) distances to the source. CONCLUSIONS: The modular spacer represents an important addition to the planning and treatment stages of mobile tongue cancer using HDR-ISBT.

A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation.

Several hormones and growth factors, including adipokines, play important roles during muscle development and regeneration. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 is a novel adipokine previously reported to reduce glucose output in hepatocytes and lower glucose levels in mice models. In the present study, we provide the first evidence for a physiological role of the CTRP3 in myogenesis using C2C12 myoblasts. CTRP3 was expressed in developing skeletal muscle tissues, and the expression level of CTRP3 was increased during myogenic differentiation of C2C12 cells. Recombinant CTRP3 (rCTRP3) promoted the proliferation of undifferentiated C2C12 myoblasts and this response required activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In contrary, rCTRP3 inhibited myogenic differentiation and fusion of C2C12 cells by suppressing the expression of myogenic marker genes (myogenin and myosin heavy chain). CTRP3 mRNA expression was increased in C2C12 myoblasts treated with transforming growth factor-ß3 (TGF-ß3), suggesting that TGF-ß3 is one of the extracellular factors regulating CTRP3 expression during myogenesis. These results indicate a novel physiological role for CTRP3 during skeletal myogenesis.

Evaluation of the scatter doses in the direction of the buccal mucosa from dental metals.

The presence of dental metals creates radiation dose perturbation due to scattered radiation during radiation therapy for the head and neck region. The purpose of our study was to compare the scatter doses resulting from various dental metals in the direction of the buccal mucosa among a single-field technique, three-dimensional conformal radiation therapy (3D CRT), and intensity-modulated radiation therapy (IMRT) during radiation therapy for the head and neck region. We used nine metal cubes with 10 mm sides, which were placed inside a water phantom. The scatter doses from the cubes in the direction of the buccal mucosa were measured using radiochromic films. The films were placed perpendicularly to the surface of the cubes. The phantom was irradiated with a 4 MV photon energy by a linear accelerator for all techniques. In the single-field technique, the scatter doses from dental metals showed 3.7%-19.3% dose increases, and gold showed the largest dose increase. In 3D CRT, the scatter doses from dental metals showed 1.4%-6.9% dose increases, which were within the measurement uncertainty (except for gold). In IMRT, the scatter doses from dental metals showed only 1.4%-4.3% dose increases, which were all within the measurement uncertainty. During radiation therapy for the head and neck region, the scatter doses from the tested dental metals in the direction of the buccal mucosa in 3D CRT or IMRT were lower than those using the single-field technique. However, there were no differences between the scatter doses resulting from particular dental metals in the direction of the buccal mucosa in 3D CRT and those in IMRT, except for gold.

Influence of an object's z-axis location and location on the axial plane on the voxel value representation and uniformity in cone beam computed tomography.

OBJECTIVE: This study aimed to determine the influence of an object's z-axis location and location on the axial plane on the voxel values in cone beam computed tomography. STUDY DESIGN: The CTP401 and CTP486 of the Catphan 500 phantom were scanned with an Alphard-3030 at 6 locations in the z-axis. RESULTS: In CTP401, the voxel values of 3 inserts showed the lowest values when the center of the radiation field corresponded to under 2 or 4 cm of the z-axis center of CTP401. In CTP486, the voxel values showed the lowest values when the center of the radiation field corresponded to under 2 or 4 cm of the z-axis center of CTP486. On the same axial plane, the voxel values at the center showed significantly lower values than the off-center locations (P = .002). CONCLUSIONS: The voxel values in the Alphard-3030 changed based on the z-axis location of the radiation field and were nonuniform on the same axial plane.

Diffuse large B-cell lymphoma of the mandible with periosteal reaction: a case report.

This report describes a rare case of a 63-year-old man with a lymphoma in the right mandibular ramus with periosteal reaction. Computed tomography (CT) images showed a soft tissue density (28 × 48 × 32 mm) around the right mandibular foramen. Bone-mode CT images showed diffuse bone destruction of the right mandibular ramus. Moreover, a periosteal reaction was seen on the lingual cortical bone of the right mandibular ramus. Histopathologic examination found a diffuse large B-cell lymphoma.

Evaluation of imaging performance of megavoltage cone-beam CT over an extended period.

A linear accelerator vendor and the AAPM TG-142 report propose that quality assurance testing for image-guided devices such megavoltage cone-beam CT (MV-CBCT) be conducted on a monthly basis. In clinical settings, however, unpredictable errors such as image artifacts can occur even when quality assurance results performed at this frequency are within tolerance limits. Here, we evaluated the imaging performance of MV-CBCT on a weekly basis for ∼ 1 year using a Siemens ONCOR machine with a 6-MV X-ray and an image-quality phantom. Image acquisition was undertaken using 15 monitor units. Geometric distortion was evaluated with beads evenly distributed in the phantom, and the results were compared with the expected position in three dimensions. Image-quality characteristics of the system were measured and assessed qualitatively and quantitatively, including image noise and uniformity, low-contrast resolution, high-contrast resolution and spatial resolution. All evaluations were performed 100 times each. For geometric distortion, deviation between the measured and expected values was within the tolerance limit of 2 mm. However, a subtle systematic error was found which meant that the phantom was rotated slightly in a clockwise manner, possibly due to geometry calibration of the MV-CBCT system. Regarding image noise and uniformity, two incidents over tolerance occurred in 100 measurements. This phenomenon disappeared after dose calibration of beam output for MV-CBCT. In contrast, all results for low-contrast resolution, high-contrast resolution and spatial resolution were within their respective tolerances.

Temporomandibular joints in patients with rheumatoid arthritis using magnetic resonance imaging.

The aim of this study was to determine the relationship between the pathogenic duration of rheumatoid arthritis in joints other than the temporomandibular joint and bone and soft tissue involvement of the temporomandibular joint using magnetic resonance imaging. Twenty-six symptomatic patients diagnosed with rheumatoid arthritis were enrolled in this study. All patients were classified according to the duration of rheumatoid arthritis in joints other than the temporomandibular joint. The relationships between the duration of rheumatoid arthritis in these various joints and magnetic resonance findings in the temporomandibular joint were analyzed using the chi-square test. Bony changes in the mandibular condyle were observed in 43 of 52 (82.7 %) temporomandibular joints, but the frequency of such changes was not significantly correlated with the duration of rheumatoid arthritis in other joints. We found a significant correlation between the duration of rheumatoid arthritis in other joints and the type and number of bony changes in the mandibular condyle (P < 0.05). Superior disc positions were observed in 27 of 52 (51.9 %) temporomandibular joints. T2-weighted images demonstrated effusion in the joint space in 38 of 52 (73.1 %) temporomandibular joints. A biplanar disc configuration was the most frequent configuration in all groups. The duration of rheumatoid arthritis in other joints was significantly correlated with the mobility of the mandibular condyle (P < 0.05). The type and number of bony changes and mobility of the mandibular condyle showed significant relationships with the duration of rheumatoid arthritis in other joints in the body (P < 0.05).

A novel adipokine C1q/TNF-related protein 1 (CTRP1) regulates chondrocyte proliferation and maturation through the ERK1/2 signaling pathway.

Adipose tissue-derived adipokines play important roles as regulators of skeletal growth and development. CTRP1, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. It is expressed at high levels in adipose tissue and has recently emerged as a novel adipokine. In the present study, we provide the first evidence for a physiological role of the CTRP1 in chondrocyte proliferation and maturation using a mouse chondrocytic cell line, N1511. The CTRP1 protein was strongly expressed and predominantly distributed in the reserve and proliferative chondrocytes in the fetal growth plate and its mRNA decreased during the maturation of N1511 chondrocytes. Recombinant CTRP1 promoted proliferation of immature proliferating N1511 chondrocytes in a dose-dependent manner, whereas it inhibited maturation of maturing N1511 chondrocytes. The stimulatory effect of CTRP1 on chondrocyte proliferation was associated with activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway. On the other hand, the inhibitory effect of CTRP1 on chondrocyte maturation is associated with suppression of the ERK1/2 pathway. These results suggest a novel physiological role for CTRP1 in endochondral ossification.

Contrast-enhanced multidetector computerized tomography for odontogenic cysts and cystic-appearing tumors of the jaws: is it useful?

OBJECTIVE: The purpose of this study was to investigate the usefulness of computerized tomography (CT), particularly contrast-enhanced CT, in differentiation of jaw cysts and cystic-appearing tumors. STUDY DESIGN: We retrospectively analyzed contrast-enhanced CT images of 90 patients with odontogenic jaw cysts or cystic-appearing tumors. The lesion size and CT values were measured and the short axis to long axis (S/L) ratio, contrast enhancement (CE) ratio, and standard deviation ratio were calculated. RESULTS: The lesion size and the S/L ratio of keratocystic odontogenic tumors were significantly different from those of radicular cysts and follicular cysts. There were no significant differences in the CE ratio among the lesions. CONCLUSIONS: Multidetector CT provided diagnostic information about the size of odontogenic cysts and cystic-appearing tumors of the jaws that was related to the lesion type, but showed no relation between CE ratio and the type of these lesions.

High dose rate brachytherapy for oral cancer.

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer.

To compare the effects of 60 Gy/10 fractions (twice a day) with those of 54 Gy/9 fractions in high-dose-rate interstitial brachytherapy (HDR-ISBT) for early tongue cancer, we performed a matched-pair analysis of patients with early tongue cancer (T1-2N0M0), who were treated with 60 or 54 Gy of radiation between 1996 and 2004. Seventeen patients treated with 54 Gy and 34 matched-pair patients treated with 60 Gy were extracted and analyzed. Local recurrence occurred in two patients in the 54-Gy arm and five patients in the 60-Gy arm. The 2-year local control rates were 88% for both the 54-Gy arm and 60-Gy arm (not significant). The 2-year overall survival rates were 88% in the 60-Gy arm and 82% in the 54-Gy arm. Two-year actuarial complication-free rates were 91% in the 60-Gy arm and 83% in the 54-Gy arm (not significant), respectively. There was no significant association between the total dose and local control rate and late complications. The outcome of 54 Gy/ 9 fractions was similar to that of 60 Gy/ 10 fractions in patients with early tongue cancer.

The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway.

CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. It is expressed at high levels in adipose tissue and has recently emerged as a novel adipokine. In the present study, we provide the first evidence for a physiological role of the new adipokine, CTRP3, in the reproductive system. CTRP3 was specifically expressed in interstitial Leydig cells, where testosterone is produced, in the adult mouse testis. CTRP3 increased testosterone production by TM3 mouse Leydig cells in a dose-dependent manner. The increased testosterone production was linked to upregulation of steroidogenic proteins expression, such as steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage cytochrome P450 (P450scc). Moreover, increases in intracellular cyclic AMP (cAMP) concentrations and the phosphorylation of cAMP-response element binding protein (CREB) in CTRP3-stimulated TM3 Leydig cells were observed. Inhibition of this signaling pathway by a specific protein kinase A (PKA) inhibitor, H89, blocked testosterone production in CTRP3-stimulated Leydig cells, suggesting that the stimulatory effect of CTRP3 on testosterone production is associated with activation of the cAMP/PKA signaling pathway. Thus, our results demonstrate a physiological role for CTRP3 in testicular steroidogenesis and provide novel insights in the intracellular mechanisms activated by this protein.

Electron beam radiotherapy for tongue cancer using an intra-oral cone.

To explain the adaptation technique using an intra-oral cone (IOC) for radiation therapy, and to determine the optimal schedule resulting in a high local control rate and an acceptable complication rate using direct electron beam radiation for the treatment of tongue cancer. Thirty patients with the tongue cancer (T1:T2:T3=16:11:3) were treated with 6-15 MeV electron radiation using an IOC. Twenty-six patients were treated with electron radiation using an IOC with or without an excisional biopsy. The other four patients were treated with a combination of the external beam radiation and electron radiation using the IOC. In order to formulate a safe and effective treatment program, we calculated the biologically effective dose (BED). The two- and five-year local control rates for all patients were 63% and 52%, respectively. The two- and five-year overall survival rates for all patients were 73% and 69%, respectively. Local control was achieved in 12 of 15 patients who were irradiated with a BED of 90.9 Gy(10) or more, whereas it was not achieved in nine of the 15 patients who were treated with less than a BED of 90.9 Gy(10) (p=0.03). The application of electron radiation using an IOC for the treatment of tongue cancer provides acceptable local control and adverse effect rates, especially for elderly patients considered to be high risk for complications from anesthesia. The optimum BED(10) value for the treatment of early tongue cancer using the IOC technique appears to be at least 90.9 Gy(10).

Radiographic features of a patient with both cemento-ossifying fibroma and keratocystic odontogenic tumor in the mandible: a case report and review of literature.

We herein describe a rare case of a 48-year-old woman with both ossifying fibroma (OF) and keratocystic odontogenic tumor (KCOT) in the mandible. CT images showed a 15 × 15 × 20-mm radiolucent-radiopaque lesion with bucco-lingual bony expansion in the left first premolar equivalent area of the mandible, and a 15 × 40 × 35-mm well-defined unilocular radiolucent lesion in the left side of the mandible, extending from the distal side of the distal root of the left second molar to the left mandibular ramus. A biopsy of the radiolucent-radiopaque lesion and fenestration surgery of the radiolucent lesion were performed. Histopathologic examination revealed a fibro-osseous lesion (FOL) and a KCOT, respectively. CT was useful in diagnosing the radiolucent-radiopaque lesion as OF and for detecting the 3-dimensional bone expansion and the contents in the lumen of the KCOT.

Correlation between pixel values in a cone-beam computed tomographic scanner and the computed tomographic values in a multidetector row computed tomographic scanner.

OBJECTIVES: The study's objectives were to investigate the correlation between pixel values obtained from a cone-beam computed tomographic (CBCT) scanner and the computed tomographic (CT) values from a multidetector row CT scanner and to determine whether they have a linear relationship at various tube voltages and tube currents. METHODS: A phantom with different concentrations of contrast medium at the center of a multidetector row CT and a CBCT scanner was scanned at various imaging parameters. Computed tomographic values and pixel values were measured using ImageJ. Regression analysis was performed, as well as correlation tests with a Pearson correlation coefficient. RESULTS: A significant correlation between pixel values and the CT values of the same specimen was observed (P < 0.0001), and a linear relationship was found between the values from the 2 scanners at each parameter. CONCLUSIONS: A high correlation and linear relationship between the CT values and pixel values were found at each parameter. Therefore, linear functions can be used to convert a pixel value from the CBCT machine used in this study to the CT values.

Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older.

BACKGROUND: To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number. METHODS: We examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart. RESULTS: Definitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years. CONCLUSION: Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.

A case report of primary gingival angiosarcoma.

Angiosarcoma is a rare malignant neoplasm and primary angiosarcoma is extremely rare. This study reports clinico-pathological features and CT image finding of a case of primary angiosarcoma in the upper gingival and a review of previously reported cases of primary gingival angiosarcomas including the present case.

Assessment of influence of smoking, drinking, leukoplakia and dental irritation on local control of early oral tongue carcinoma treated with brachytherapy: age and dental factors are potential prognostic factors.

BACKGROUND: To examine the background characteristics of elderly patients (65 years or older) with node-negative mobile tongue cancer (T1-2N0M0) who showed worse local control than a younger group. MATERIALS AND METHODS: We retrospectively analyzed background data for 265 patients treated with brachytherapy with or without external radiotherapy between 1967 and 1999. We examined dental factors (such as irritation by prosthesis), leukoplakia, tobacco smoking and alcohol consumption for comparisons between the elderly (age > or = 65 years; n = 83) and a control group (64 years or younger; n = 182). RESULTS: The elderly patients showed a worse outcome than the control group (respectively 86% and 70% at 5 years; P < 0.05). Incidence of dental factors tended to be higher for elderly patients (53%) than the control group (40%, P = 0.07). Dental factors proved to have prognostic importance for local control. Five-year local control rate was 85% for patients with and 76% for patients without dental factors (P = 0.04). The elderly group positive for dental factors showed a lower 5-year local control rate (61%) than the other three groups [(elderly without the dental factor (-) group (80%), control with the dental factor (+) group (84%), and control without the dental factor (-) group (87%)] (P < 0.05). Leukoplakia was found more frequently in the control (23%) than in the elderly group (5%) (P = 0.006) but had no effect on treatment outcome. CONCLUSIONS: Age and dental factors (including prosthesis irritation) are potentially important prognostic factors for local control of oral tongue cancer treated with brachytherapy, especially for elderly patients.

Elevated expression of CTRP3/cartducin contributes to promotion of osteosarcoma cell proliferation.

CTRP3/cartducin, a novel secretory protein, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily, and plays important roles in regulating both embryonic cartilage development and postnatal longitudinal bone growth. CTRP3/cartducin is expressed in human osteosarcomas. We hypothesized that CTRP3/cartducin might have a role in osteosarcoma tumor growth and metastasis. Murine osteosarcoma cell lines, NHOS and LM8, were used as a model. RT-PCR analysis showed that the mRNA level of CTRP3/cartducin was increased in these two murine osteosarcoma cell lines compared with its level in normal murine osteoblast MC3T3-E1 cells. Western blot analysis showed that the protein level of CTRP3/cartducin was also increased in these two osteosarcoma cell lines. Stimulation of NHOS and LM8 cells by CTRP3/cartducin promoted tumor cell growth but not migration in vitro. Further, CTRP3/cartducin stimulation led to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in these two osteosarcoma cell lines. MAPK/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, blocked CTRP3/cartducin-induced cell proliferation. These results suggest that CTRP3/cartducin expression may play a role in osteosarcoma tumor growth associated with activation of the ERK1/2 signaling pathway.