Tokuhiko Omatsu

Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells

Homeobox‐containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription‐regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue‐specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox‐containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3‐overexpressing A549 cells. In the HOXD3‐overexpressing cell lines, expression of E‐cadherin was lost and plakoglobin was strongly repressed, whereas integrin α3 and β3 were up‐regulated and N‐cadherin and integrin α4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3‐overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti‐integrin β1 and β3 suggested that the increased haptotaxis of the HOXD3‐overexpressing cells to vitronectin resulted from increased expression and activation of integrin αvβ3, and that overexpression of the HOXD3 gene converted the integrin β1‐dependent haptotaxis to fibronectin into both integrin β1‐ and β3‐dependent one. HOXD3 overexpression increased production of matrix‐degrative enzymes including matrix metalloproteinase‐2 and urokinase‐plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis‐promoting gene in human lung cancer A549 cells.

Metastases in Mediastinal and Hilar Lymph Nodes in Patients With Non-Small Cell Lung Cancer : Quantitative Assessment With Diffusion-Weighted Magnetic Resonance Imaging and Apparent Diffusion Coefficient

Objective: To evaluate diffusion-weighted magnetic resonance (DW-MR) imaging for detection of metastases in lymph nodes by using quantitative analysis. Methods: Seventy patients with non-small cell lung cancer were examined with DW and short inversion time inversion recovery (STIR) turbo-spin-echo MR imaging. Apparent diffusion coefficient of each lung cancer and lymph node was calculated from DW-MR images. Difference of the apparent diffusion coefficient in a lung cancer and a lymph node was calculated (D1). From STIR turbo-spin-echo MR images, ratios of signal intensity in a lymph node to that in a 0.9% saline phantom was calculated (lymph node-saline ratio [LSR1]). For quantitative analysis, the threshold value for a positive test was determined on a per node basis and tested for ability to enable a correct diagnosis on a per patient basis. Results of quantitative analyses of DW- and STIR-MR images were compared on a per patient basis with McNemar testing. Results: Mean D1 in the lymph node group with metastases was lower than that in the group without metastases (P < 0.001). When an D1 of 0.24 × 10−3 mm2/s was used as the positive test threshold, sensitivity, specificity, and accuracy were 69.2%, 100%, and 94.0%, respectively, on a per patient basis. There was no significant difference (P > 0.05) between quantitative analyses of DW-MR images and STIR-MR images. Conclusions: Quantitative analysis of DW-MR images enables differentiation of lymph nodes with metastasis from those without.

The role of radiotherapy in treating squamous cell carcinoma of the external auditory canal, especially in early stages of disease

PURPOSE Our intent was to investigate the role of radiotherapy in treating external auditory canal squamous cell carcinoma, especially in early stages of disease. MATERIALS AND METHODS The treatment results for 20 patients treated between 1980 and 1998 were retrospectively analyzed. Radiotherapy was used as an initial treatment without surgery in eight patients and with surgery in 12 patients. The patients treated by radiotherapy alone received 65 Gy in 26 fractions over 6.5 weeks. The patients treated with radiotherapy perioperatively received 30-75 Gy in 12-30 fractions. The follow-up period for survivors including patients died of intercurrent disease ranged from 7 to 205 months (mean: 71 months). RESULTS The 5-year survival rate calculated by the Kaplan-Meier method for all patients was 59%. According to Stell classification (Laryncol. Otol. 99 (1985) 847), the 5-year survival rates for eight patients with T1 disease and eight with T2 disease were 100 and 38%, respectively. In the eight patients with T1 disease, disease control was 100%. Local control with hearing preservation was achieved in five patients with T1 disease by radiotherapy alone. No late complications related to radiotherapy were observed. CONCLUSIONS A precise diagnosis of the disease in terms of whether or not it has invaded the bone is important in order to predict the treatment outcome. Radiotherapy with or without surgery is the treatment of choice for patients with T1-stage disease. Surgery with radiotherapy is recommended as standard care for tumors with bony invasion.

Three-Dimensional Intrafractional Motion of Breast During Tangential Breast Irradiation Monitored With High-Sampling Frequency Using a Real-Time Tumor-Tracking Radiotherapy System

PURPOSE To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. METHODS AND MATERIALS A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. RESULTS The mean +/- standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95% CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95% CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. CONCLUSION Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution.

Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry

PURPOSE To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. METHOD Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using (99m)Tc-DMSA scintigraphy was also investigated. RESULTS The time required for volumetry of bilateral kidneys with the newly developed software (16.7±3.9s) was significantly shorter than that of the workstation (102.6±38.9s, p<0.0001). The results of n-SRV (49.7±4.0%) were highly consistent with those of z-SRV (49.9±3.6%), with a mean discrepancy of 0.12±0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25±1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). CONCLUSION The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors.

Splenic volume measurements on computed tomography utilizing automatically contouring software and its relationship with age, gender, and anthropometric parameters.

OBJECTIVE The present research was conducted to establish the normal splenic volume in adults using a novel and fast technique. The relationship between splenic volume and age, gender, and anthropometric parameters was also examined. MATERIALS AND METHODS The splenic volume was measured in 230 consecutive patients who underwent computed tomography (CT) scans for various indications. Patients with conditions that have known effect on the spleen size were not included in this study. A new technique using volumetric software to automatically contour the spleen in each CT slice and quickly calculate splenic volume was employed. Inter- and intra-observer variability were also examined. RESULTS The average splenic volume of all the subjects was 127.4+/-62.9 cm(3), ranging from 22 to 417 cm(3). The splenic volume (S) correlated with age (A) (r=-0.33, p<0.0001), body weight (W) (r=0.35, p<0.0001), body mass index (r=0.24, p<0.0001) and body surface area (BSA) (r=0.31, p<0.0001). The age-adjusted splenic volume index correlated with gender (p=0.0089). The formulae S=W[6.47A(-0.31)] and S=BSA[278A(-0.36)] were derived and can be used to estimate the splenic volume. Inter- and intra-observer variability were 6.4+/-9.8% and 2.8+/-3.5% respectively. CONCLUSION Of the anthropometric parameters, the splenic volume was most closely linked to body weight. The automatically contouring software as well as formulae can be used to obtain the volume of the spleen in regular practice.

Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells

Unmethylated cytosine‐phosphorothioate‐guanine containing oligodeoxynucleotides (CpG‐ODN) is known as a ligand of toll‐like receptor 9 (TLR9), which selectively activates type‐1 immunity. We have already reported that the vaccination of tumor‐bearing mice with liposome‐CpG coencapsulated with model‐tumor antigen, ovalbumin (OVA) (CpG + OVA‐liposome) caused complete cure of the mice bearing OVA‐expressing EG‐7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)‐OVA‐carcinoma. To overcome the refractoriness of LLC‐OVA, we tried the combination therapy of radiation with CpG‐based tumor vaccination. When LLC‐OVA‐carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7–8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA‐liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA‐liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA‐liposome allowed the augmented induction of OVA‐tetramer+ LLC‐OVA‐specific cytotoxic T lymphocyte (CTL) in DLN of tumor‐bearing mice. These results indicate that the combined therapy of radiation with CpG‐based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934–939)

Prenatal diagnosis of short-rib polydactyly syndrome type 3 (Verma-Naumoff type) by three-dimensional helical computed tomography

We present a case of short‐rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D‐CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis‐van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D‐CT in the early third trimester to examine a fetus suggested to have phenotypes of ‘short‐rib dysplasia group’ on ultrasonography. 3D‐CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short‐rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D‐CT for the precise prenatal diagnosis of skeletal dysplasias.

Wavelet compression on detection of brain lesions with magnetic resonance imaging.

The purpose of this report is to assess clinically acceptable compression ratios on the detection of brain lesions at magnetic resonance imaging (MRI). Four consecutive T2-weighted and the corresponding T1-weighted images obtained in 20 patients were studied for 109 anatomic sites including 50 with lesions and 59 without lesions. The images were obtained on a 1.5-T MR unit with a pixel size of 0.9 to 1.2×0.47 mm and a section thickness of 5 mm. The image data were compressed by wavelet-based algorithm at ratios of 20∶1, 40∶1, and 60∶1. Three radiologists reviewed these images on an interactive workstation and rated the presence or absence of a lesion with a 50 point scale for each anatomic site. The authors also evaluated the influence of pixel size on the quality of image compression. At receiver operating characteristic (ROC) analysis, no statistically significant difference was detected at a compression ratio of 20∶1. A significant difference was observed with 40∶1 compressed images for one reader (P=.023), and with 60∶1 for all readers (P=.001 to .012). A root mean squared error (RMSE) was higher in 0.94-×0.94-mm pixel size images than in 0.94-×0.47-mm pixel size images at any compression ratio, indicating compression tolerance is lower for the larger pixel size images. The RMSE, subjective image quality, and error images of 10∶1 compressed 0.94-×0.94-mm pixel size images were comparable with those of 20∶1 compressed 0.94-×0.47-mm pixel size images. Wavelet compression can be acceptable clinically at ratios as high as 20∶1 for brain MR images when a pixel size at image acquisition is around 1.0×0.5 mm, and as high as 10∶1 for those with a pixel size around 1.0×1.0 mm.

Intravenous pyogenic granuloma of the finger

Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.