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author:("Takada, hideo")
1.  Promoting effect of arachidonic acid supplementation on N-methyl-N-nitrosourea-induced pancreatic acinar cell hyperplasia in young Lewis rats 
Oncology Letters  2012;5(1):76-82.
Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standard of Codex Alimentarius. However, few studies have been performed that are concerned with the possible carcinogenic effects of AA supplementation during neonatal life. The effect of dietary AA supplementation in dams, during gestation and lactation, was investigated in N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the exocrine pancreas of young Lewis rats. Dams were fed either an AA (2.0% AA) or a basal (<0.01% AA) diet. On postnatal day 0 (at birth), male and female pups received a single intraperitoneal injection of either 35 mg/kg MNU or vehicle. The morphology and proliferating activity of the exocrine pancreas were examined by proliferative cell nuclear antigen immunohistochemistry 7, 14, 21, 28 and/or 60 days post-MNU. Histopathologically, acinar cell hyperplasia (ACH) occurred in the MNU-treated groups 60 days after MNU injection, irrespecitive of whether the rats had been fed an AA diet. Morphometrically, the number and area of ACH per 1 mm2 in MNU-treated rats increased significantly in the AA diet-fed rats, compared with basal diet-fed rats. The number of proliferative cell nuclear antigen-positive acinar cells in both the normal and hyperplastic areas of MNU-treated rats increased significantly in the AA diet-fed rats. In conclusion, providing dams with an AA-rich diet during gestation and lactation promotes MNU-induced pancreatic ACH in young Lewis rats.
doi:10.3892/ol.2012.1009
PMCID: PMC3525495  PMID: 23255898
arachidonic acid; fatty acids; N-methyl-N-nitrosourea; pancreas; acinar cell; hyperplasia; rats
2.  Peroxidation of n-3 Polyunsaturated Fatty Acids Inhibits the Induction of iNOS Gene Expression in Proinflammatory Cytokine-Stimulated Hepatocytes 
Eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA), n-3 polyunsaturated fatty acids (PUFAs), have a variety of biological activities including anti-inflammatory and anticancer effects. We hypothesized that their peroxidized products contributed in part to anti-inflammatory effects. In the liver, the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as one of the factors in hepatic inflammation and injury. We examined whether the peroxidation of EPA/DHA influences the induction of iNOS and NO production in proinflammatory cytokine-stimulated cultured hepatocytes, which is in vitro liver inflammation model. Peroxidized EPA/DHA inhibited the induction of iNOS and NO production in parallel with the increased levels of their peroxidation, whereas unoxidized EPA/DHA had no effects at all. Peroxidized EPA/DHA reduced the activation of transcription factor, NF-κB, and the expression of the iNOS antisense transcript, which are involved in iNOS promoter transactivation (mRNA synthesis) and its mRNA stabilization, respectively. These findings demonstrated that peroxidized products of EPA/DHA suppressed the induction of iNOS gene expression through both of the transcriptional and posttranscriptional steps, leading to the prevention of hepatic inflammation.
doi:10.1155/2011/374542
PMCID: PMC3136170  PMID: 21773019
3.  Well-Differentiated Liposarcoma, an Atypical Lipomatous Tumor, of the Mesentery: A Case Report and Review of the Literature 
Case Reports in Oncology  2011;4(1):178-185.
Mesenteric liposarcoma is a rare neoplasm. Here, we report the case of a 73-year-old Japanese man with a well-differentiated (WD) liposarcoma of the mesentery. Due to rapid growth of the abdominal mass and abdominal insufficiency, a tumorectomy was performed. The excised tumor was 12.4 × 9.6 cm in size and weighed 548 g. Cut sections showed a lobulated yellow and/or grayish-colored appearance. The histological features were predominantly those of the sclerotic and lipoma-like variants of WD liposarcoma. The cytoplasm of most spindle cells was diffusely immunoreactive for CD34, while fat cells were positive for S-100 protein. Some spindle cell nuclei were positive for CDK4, and a few were positive for MDM2. The average Ki-67 proliferation index in tumor cells was 10%, and androgen receptor expression was detected in tumor cell nuclei. The present case and 11 cases identified from a literature search were reviewed. The WD mesenteric liposarcomas developed in patients in the fourth to seventh decades of life (mean age 57.9 years). The patients consisted of 7 men and 5 women. All tumors were larger than 10 cm in diameter at the time of surgery. Complete resection might be the only curative therapy for WD liposarcomas of the mesentery, but long-term follow-up is needed because of the possibility of a local recurrence of the tumor.
doi:10.1159/000327266
PMCID: PMC3081650  PMID: 21526137
Well-differentiated liposarcoma; Atypical lipomatous tumor; Mesentery; CD34; CDK4; MDM2; Androgen receptor; Immunohistochemistry
4.  Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report 
We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.
doi:10.1159/000208375
PMCID: PMC2895173  PMID: 20651962
Primary; Carcinoid tumor; Liver
5.  Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action 
Breast Cancer Research  2004;6(4):R291-R299.
Introduction
The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA).
Methods
KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet.
Results
CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner.
Conclusion
CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.
doi:10.1186/bcr789
PMCID: PMC468623  PMID: 15217495
apoptosis; breast cancer; conjugated docosahexaenoic acid; docosahexaenoic acid; human

Results 1-5 (5)