Daisuke Komatsu

NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression

Reactive oxygen species (ROS)-generating enzyme Nox1 is important in the induction of oncogenic Ras transformation phenotypes, but it is not defined whether Nox1 is involved in Ras-induced upregulation of vascular endothelial growth factor (VEGF), a potent stimulator of tumor angiogenesis. Here we describe that ablation of the Nox1 activity by Nox1 small-interference RNAs (siRNAs) or diphenylene iodonium (DPI) inhibited synthesis of both VEGF proteins and VEGF mRNAs in K-Ras transformed normal rat kidney (KNRK) cells. Nox1siRNAs and DPI suppressed extracellular signal-regulated kinase (ERK)-dependent phosphorylation of a transcription factor Sp1 and Sp1 binding to a VEGF promoter. Furthermore, tumors derived from Nox1siRNA-transfected KNRK cells markedly decreased neovascularization. The Nox1 activity was required for VEGF production in human colon cancer CaCO-2 cells, as in the case of KNRK cells. However, since overexpression of Nox1 in normal rat kidney cells failed to induce VEGF, the Nox1 activity alone was not sufficient to upregulate VEGF expression, which suggests that unlike the previously proposed model, Nox1 may act in concert with other effectors integrated into the Ras network. We propose that Nox1 mediates oncogenic Ras-induced upregulation of VEGF and angiogenesis by activating Sp1 through Ras-ERK-dependent phosphorylation of Sp1.

Gastric schwannoma exhibiting increased fluorodeoxyglucose uptake.

This is the first case of gastric schwannoma that exhibited increased accumulation of [(18)F] fluorodeoxyglucose (FDG) on positron emission tomography (PET) imaging. The patient was a 60-year-old woman in whom esophagogastroduodenoscopy showed a submucosal tumor, about 25 mm in size, in the upper body of the stomach, with ulceration at the top of the tumor. Endoscopic ultrasonography revealed a well-defined hypoechoic mass located in the proper muscle layer of the stomach. The specimen taken from the tumor showed only inflammatory degenerative tissue. Abdominal computed tomography revealed a tumor in the upper body of the stomach. FDG-PET showed FDG uptake (standardized uptake value [SUV] max 5.8) coincident with the tumor. Hence, the tumor was diagnosed initially as a gastrointestinal stromal tumor of the stomach. Laparoscopic partial gastrectomy was performed. Pathological examination showed that the tumor consisted of spindle cells with large nuclei, and mitosis was absent. The Ki-67 labeling index of the tumor cells was 4%. Immunohistochemically, the tumor cells showed a positive reaction for S-100 protein, whereas they were negative for KIT, CD 34, and alpha-smooth muscle actin protein. The tumor was diagnosed as a benign gastric schwannoma. Gastric schwannoma should be included in the differential diagnosis of submucosal tumors of the stomach with FDG uptake.

Granulocyte colony stimulating factor-producing collision tumor of the gastric cardia

Patients with various kinds of nonhematopoietic tumors occasionally have associated leukocytosis without overt inflamation. This has been shown to be due to granulocyte colony-stimulating factor (G-CSF) produced by the tumor cells themselves. G-CSF production has been observed in several types of malignancy, including cancer of the digestive organs.1 We report here a patient with a collision tumor of the gastric cardia, consisting of a G-CSFproducing-squamous cell carcinoma (SCC) of the esophagus and an adenocarcinoma (AD) of the stomach, who had a good clinical outcome. A 73-year-old man was admitted complaning of dysphagia. Laboratory examinations showed extensive leukocytosis (45710/μl with 91.6% neutrophils). The serum level of G-CSF was markedly elevated, to 231pg/ml (normal range, 9.8pg/ml). The serum levels of SCC antigen and carcinoembrionic antigen were 3.3ng/ml (normal range, 1.5ng/ml) and 3.2ng/ml (normal range, 5.0ng/ml), respectively. A barium meal study showed an irregularly shaped tumor in the gastric cardia, apparently invading the lower esophagus (Fig. 1). Esophagoscopy showed an elevated tumor in the lower esophagus 35cm from the incisor; however, the scope could not be inserted into the stomach due to stenosis. Histologically, biopsy specimens taken from the esophageal tumor revealed an SCC. Bone marrow aspiration biopsy revealed granulocytic hyperplasia with predominantly mature cells. The preoperative diagnosis was SCC extending from the lower esophagus to the gastric cardia, with suspected G-CSF production; thus, a proximal gastrectomy with a lower esophagectomy and regional node dissections was performed. After surgery, the leukocyte count was 6870/μl, with 68.1% neutrophils, and the serum level of G-CSF was 12pg/ml. Nineteen months after surgery, the patient was well without any recurrence. Macroscopic examination of the resected specimen showed that the tumor extended from the lower esophagus to the upper gastric

Evaluation of splenic perfusion and spleen size using dynamic computed tomography: Usefulness in assessing degree of liver fibrosis

To enhance the usefulness of splenic perfusion evaluated by means of dynamic computed tomography (CT) and spleen size in assessing the degree of liver fibrosis.

Quantitative estimation of progression of chronic liver disease using gadoxetate disodium-enhanced magnetic resonance imaging: Quantitative MR imaging in chronic liver disease

The purpose of this study was to determine whether the liver stiffness (LS) measured on magnetic resonance (MR) elastography can be estimated by a combination of gadoxetate disodium‐enhanced MR imaging (EOB‐MRI) and ordinary blood tests.

Compartment model analysis of intravenous contrast-enhanced dynamic computed tomography in hepatic hemodynamics: A validation study using intra-arterial contrast-enhanced computed tomography: Validation of hepatic CT perfusion study

To verify the utility of the 2‐in‐1‐out‐compartment model analysis (CMA) of intravenous contrast‐enhanced dynamic computed tomography (IV‐CT) for evaluating hepatic arterial and portal venous flow using intra‐arterial contrast‐enhanced CT (IA‐CT).