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Takata A.,University of Tokyo | Otsuka M.,University of Tokyo | Yoshikawa T.,University of Tokyo | Kishikawa T.,University of Tokyo | And 11 more authors.
Hepatology | Year: 2013

MicroRNAs (miRNAs) are small RNAs that regulate the expression of specific target genes. While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown. We investigated whether deregulation of miRNA machinery components and subsequent functional impairment of miRNAs are involved in hepatocarcinogenesis. Among miRNA-containing ribonucleoprotein complex components, reduced expression of DDX20 was frequently observed in human hepatocellular carcinomas, in which enhanced nuclear factor-κB (NF-κB) activity is believed to be closely linked to carcinogenesis. Because DDX20 normally suppresses NF-κB activity by preferentially regulating the function of the NF-κB-suppressing miRNA-140, we hypothesized that impairment of miRNA-140 function may be involved in hepatocarcinogenesis. DNA methyltransferase 1 (Dnmt1) was identified as a direct target of miRNA-140, and increased Dnmt1 expression in DDX20-deficient cells hypermethylated the promoters of metallothionein genes, resulting in decreased metallothionein expression leading to enhanced NF-κB activity. MiRNA-140-knockout mice were prone to hepatocarcinogenesis and had a phenotype similar to that of DDX20 deficiency, suggesting that miRNA-140 plays a central role in DDX20 deficiency-related pathogenesis. Conclusion: These results indicate that miRNA-140 acts as a liver tumor suppressor, and that impairment of miRNA-140 function due to a deficiency of DDX20, a miRNA machinery component, could lead to hepatocarcinogenesis. (HEPATOLOGY 2013) © 2012 American Association for the Study of Liver Diseases. Source


Nakahara D.,Juntendo University | Yonezawa I.,Juntendo University | Kobanawa K.,Kyoundo Hospital | Sakoda J.,Juntendo University | And 4 more authors.
Spine | Year: 2011

STUDY DESIGN. A prospective study of magnetic resonance imaging findings in outpatients with idiopathic scoliosis. OBJECTIVE. The purpose of this study was to determine the prevalence of neural axis abnormalities in outpatients with scoliosis and to analyze the characteristics of patients who had such abnormalities. SUMMARY OF BACKGROUND DATA. In previous studies, neural axis abnormalities were found in 2.9% to 37% of patients with idiopathic scoliosis. The current guidelines for MRI screening in scoliosis are valuable, and the proposed indications for performing MRI in the literature include early onset, atypical curvature, double thoracic curve (King type-5), rapid progression, male gender, and abnormal neurologic findings. METHODS. A total of 472 outpatients with a primary diagnosis of idiopathic scoliosis were examined for neural axis abnormalities by magnetic resonance imaging. Logistic regression was used to determine significant predictors of neural axis abnormalities on MRI. RESULTS. The incidence of neural axis abnormalities on MRI was 3.8% (18 of 472 patients). Among the 18 patients, 6 had a Chiari I malformation alone, 10 had a Chiari I malformation combined with syringomyelia, and 2 had a syringomyelia without Chiari I malformation. Male gender, patients younger than 11 years old, and abnormal superficial abdominal reflexes were significantly associated with the detection of neural axis abnormalities on MRI. CONCLUSION. We recommend routine use of MRI in male patients, younger than 11 years old, and abnormal superficial abdominal reflexes. Even if a patient has no specific indications for MRI, we recommend its routine use in preoperative planning. © 2011 Lippincott Williams & Wilkins, Inc. Source


Herein, we report a case in which intractable pain caused by pancreatic cancer with bone metastasis was improved by palliative radiation therapy. A 63-year-old woman was diagnosed with advanced pancreatic cancer with liver and lung metastasis and received systemic chemotherapy of S-1 combined with gemcitabine. Two months after the start of chemotherapy, the patient developed bone metastasis at the 7th cervical vertebra with severe right hand pain. Even after receiving combined modality therapy for the pain caused by bone metastasis, including administration of oxycodone, she continued to experience pain due to the bone metastasis. However, the pain improved considerably after palliative radiation therapy at a dose of 37.5 Gy/15 Fr. The patient remains free of pain due to bone metastasis 5 months after the palliative radiation therapy. We believe that palliative radiation therapy still plays an important role in the improvement of opioid-resistant intractable pain caused by bone metastasis. Source


Miura S.,Kyoundo Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012

A 65-year-old man presented with epigastralgia in our department. Contrast-enhanced computed tomography scan showed a large cystic tumor of about 12 cm in diameter attached to the gastric antrum and transverse colon. Gastric endoscopy revealed type 2 advanced gastric cancer located at the greater curvature of the antrum, and the posterior wall of the stomach was pressed from the outside. The result of tumor biopsy was adenocarcinoma. Positron emission tomography -computed tomography showed a markedly increased uptake of fluorodeoxyglucose to the tumor. With a diagnosis of extragastric growth type carcinoma of the stomach with cystic change, a distal gastrectomy, D1+lymph node dissection, and partial resection of the transverse colon was performed. A histological examination of the specimen confirmed tub2- por1, medullary type, INF b, se, ly0, v1, n0 in stage IIb, and no infiltration to the transverse colon. His postoperative course was uneventful 12 months after operation. Source


Uchino K.,University of Tokyo | Tateishi R.,University of Tokyo | Shiina S.,University of Tokyo | Kanda M.,Kyoundo Hospital | And 6 more authors.
Cancer | Year: 2011

BACKGROUND: Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease. METHODS: In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow-up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split-sample method with a testing set and a training set. RESULTS: The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03-108.7 months). In univariate analysis of the training set (n = 171), performance status, Child-Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α-fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73. CONCLUSIONS: The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis. © 2011 American Cancer Society. Source

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