Kyo S.,Kanazawa University |
Sakaguchi J.,Kanazawa University |
Kiyono T.,National Cancer Center Research Institute |
Shimizu Y.,Mochida Pharmaceutical Co. |
And 8 more authors.
Clinical Cancer Research | Year: 2011
Purpose and experimental design: Despite the therapeutic utility of progestin in invasive and preinvasive endometrial neoplasias, the molecular mechanisms through which it exerts inhibitory effects on endometrial epithelial growth are largely unknown. The aim of the study was to clarify the molecular mechanisms of progestin action to endometrial epithelial cells using originally established in vitro and in vivo treatment models for immortalized and transformed endometrial epithelial cell lines that express progesterone receptor. Results: In this model, progestin effectively inhibited the cell growth, inducing G0/G1 arrest rather than apoptosis without p21/WAF-1 induction. Using DNA microarray analysis, we identified 24 genes whose expression increased more than 10-fold on progestin treatment. Of these genes, we paid special attention to forkhead box transcription factor FOXO1, known as a key gene for endometrial decidualization. Progestin markedly induced FOXO1 gene expression mainly in the nuclei in vitro and in vivo. This induction was not due to the canonical activation of FOXO1 via protein dephosphorylation but due to FOXO1 promoter activation and mRNA induction. siRNA inhibition of FOXO1 significantly attenuated the effects of progestin to inhibit endometrial epithelial cell growth. Disrupting Akt activity by the introduction of the dominant negative form of Akt increased nuclear FOXO1 accumulation and enhanced the effect of progestin. Conclusion: These findings suggest that FOXO1 is a direct target of progestin, implicating novel molecular mechanisms of progestin to eradicate endometrial neoplasia. ©2010 AACR.
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.
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.
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.
Kawamoto J.,Kyoundo Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012
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.
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.
Takahashi E.,Kyoundo Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2011
A 43-year-old female was diagnosed with a recurrence of thymoma 6 years after the operation. Eight kinds of systemic chemotherapy were undergone for over 6 years. As the 9th chemotherapy, erlotinib hydrochloride was prescribed and the tumor decreased in size about 8 weeks later.
PubMed | Kyoundo Hospital
Type: Journal Article | Journal: Acta cytologica | Year: 2016
To determine the associations between breast cancer recurrence and cytological findings of fine-needle aspiration cytology (FNAC).The study included 117 women who had undergone a modified radical mastectomy for invasive ductal carcinoma of the breast. FNAC samples of these patients were reexamined, and cytological findings, such as cellular dissociation, nuclear pleomorphism, nuclear atypia, chromatin pattern, and nuclear size, were scored. Uni- and multivariate analyses were performed to determine the prognostic significance of the cytological findings. Corresponding cancer tissues were immunostained for estrogen receptor, progesterone receptor, human epidermal growth factor 2 (HER2), p53, and E-cadherin to determine their associations with cytological findings. Coexpression of Arp2 and WAVE2 was also examined immunohistochemically as a cell locomotion signal.Cellular dissociation (p = 0.0259) and nuclear size (p = 0.0417) were significantly associated with cancer recurrence. Multivariate analysis showed that cellular dissociation and histological grade were significant independent predictors of cancer recurrence. Cellular dissociation was found to be associated with coexpression of Arp2 and WAVE2 (p = 0.0356) and HER2 (p = 0.0469).The cytological finding of cell dissociation was associated with the activation of Arp2 and WAVE2 signals and was an independent predictor of recurrence.
PubMed | Kyoundo Hospital and Juntendo University
Type: Comparative Study | Journal: European journal of orthopaedic surgery & traumatology : orthopedie traumatologie | Year: 2016
In the present study, the adaptability of the distal radioulnar joint (DRUJ) was evaluated using conventional computed tomography (CT) evaluation methods. In addition, we investigated/compared a new method to evaluate dorsal displacement of the ulnar head. Our subjects consisted of 32 healthy volunteers (64 wrists) and 11 patients (13 wrists) with extensor tendon injuries related to dorsal displacement of the ulnar head. To diagnose instability in the DRUJ based on CT scans, the radioulnar line method and the modified radioulnar line method were measured. Instability was evaluated by the new method that the ulnar head was located on the dorsal side from a line involving the peak of Listers tubercle in parallel to this baseline was regarded as showing abnormal dorsal displacement of the ulnar head. The diagnostic accuracy of each method was calculated. The sensitivities, specificities, false-positive rates, positive predictive values and the negative predictive value of new methods were better than other two methods. The new method that we recommend is simple. Based on the results of this study, an evaluation of normal/abnormal dorsal displacement of the ulnar head in the DRUJ using the new method may be useful for determining the timing of surgery.
PubMed | Kyoundo Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2016
A 71-year-old man was admitted to our hospital because of abdominal pain. An upper gastrointestinal endoscopy revealed a type 3 tumor in the lesser curvature of the gastric body. A computed tomography (CT) scan showed synchronous liver metastasis in liver S6 and S8, and a large 8a lymph node that could be encased within the common hepatic artery. The patient was diagnosed with gastric cancer with liver metastasis, Stage , and treated with chemotherapy (S-1 plus CDDP). After 3 courses, a CT scan showed that the liver metastasis in S8 was reduced in size.The one in S6 completely disappeared. The 8a lymph node was also reduced in size and revealed to be separated from the common hepatic artery. Total gastrectomy (D2) and radiofrequency ablation (RFA) for the S8 lesion were performed. The postoperative course was favorable and the patient was treated with postoperative adjuvant chemotherapy consisting of S-1. No recurrence has been observed for 17 months after diagnosis. After chemotherapy, if R0 resection is performed, surgical resection and RFA for liver metastasis may be a useful option for gastric cancer with liver metastasis.