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1.
Oncotarget ; 7(12): 14310-23, 2016 Mar 22.
Article in English | MEDLINE | ID: mdl-26872059

ABSTRACT

In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-ß stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease-died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells.


Subject(s)
Lymphoma, B-Cell/etiology , Obesity/etiology , Repressor Proteins/physiology , Spleen/pathology , Animals , Cells, Cultured , Female , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/metabolism , Obesity/pathology , Spleen/metabolism
2.
World J Surg ; 35(1): 154-8, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20931198

ABSTRACT

BACKGROUND: We reported a novel technique of sentinel lymph node (SLN) identification using fluorescence imaging of indocyanine green injection. Furthermore, to obtain safe and accurate identification of SLN during surgery, we introduce the image overlay navigation surgery and evaluate its efficacy. METHODS: This study enrolled 50 patients with a tumors <2 cm in diameter. Initially, we obtained three-dimensional (3-D) imaging from multidetector-row computed tomography (MD-CT) by volume rendering. It was projected on the patient's operative field with the clear visualization of lymph node (LN) through projector. Then, the dye of indocyanine green (ICG) was injected subdermally in the areola. Subcutaneous lymphatic channels draining from the areola to the axilla were visible by fluorescence imaging immediately. Lymphatic flow was reached after LN revealed on 3-D imaging. After incising the axillary skin on the point of LN mapping, SLN was then dissected under the guidance of fluorescence imaging with adequate adjustment of sensitivity and 3-D imaging. RESULTS: Lymphatic channels and SLN were successfully identified by Photodynamic eye (PDE) in all patients. And the sites of skin incision also were identical with the LN being demonstrated by 3-D imaging in all patients. The mean number of SLN was 3.7. The image overlay navigation surgery was visually easy to identify the location of SLN from the axillary skin. There were no intra- or postoperative complications associated with SLN identification. CONCLUSIONS: This combined navigations of fluorescence and 3-D imaging revealed more easy and effective to detect SLN intraoperatively than fluorescence imaging alone.


Subject(s)
Breast Neoplasms/pathology , Fluorescent Dyes , Indocyanine Green , Sentinel Lymph Node Biopsy/methods , Breast Neoplasms/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Lymphatic Metastasis/pathology , Sensitivity and Specificity , Tomography, X-Ray Computed
3.
Surg Laparosc Endosc Percutan Tech ; 17(4): 313-6, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17710057

ABSTRACT

We present a successful laparoscopic treatment of paraesophageal hiatal hernia with an incarceration of the pancreas and jejunum. The patient was a 75-year-old woman who had complaints of epigastric pain and dysphasia. A chest x-ray revealed a mediastinal air-fluid level. Chest computed tomography showed intestinal contents, body and tail of the pancreas, and the splenic artery within the mediastinum. At laparoscopy, jejunum was incarcerated into the mediastinal cavity through the internal hernia of transverse mesocolon. Body and tail of the pancreas and the splenic artery were also dislocated within the hernia sac. The operation time took 115 minutes. The patient tolerated a regular diet on the first postoperative day and was discharged uneventfully. There were no recurrence or abdominal symptoms during the 29-month follow-up period. In the case of asymptomatic paraesophageal hiatal hernia with incarcerating pancreas on diagnostic imagings, elective surgical treatment is required to prevent a critical outcome.


Subject(s)
Hernia, Hiatal/complications , Hernia, Hiatal/surgery , Jejunal Diseases/etiology , Laparoscopy , Pancreatic Diseases/etiology , Aged , Female , Hernia , Humans , Jejunal Diseases/surgery , Laparoscopy/methods , Pancreatic Diseases/surgery , Radiography , Splenic Artery/diagnostic imaging
4.
Int J Oncol ; 30(5): 1089-97, 2007 May.
Article in English | MEDLINE | ID: mdl-17390010

ABSTRACT

A p53 functional analysis system, which can identify the types of abnormality of p53, such as loss of function, dominant negative function, or gain of oncogenic function, is now required. In this study, we examined the functional diversity of several mutations of p53 derived from human head and neck cancer cells. The entire open reading frame of p53 cDNA was subcloned into a mammalian expression vector, pEGFP-C3, and genetic mutations were determined. Then, intracellular localization and transcriptional activity of the tumor-derived p53 proteins were examined in Saos-2 cells. A mutant-p53 (Glu17Lys, His193Leu) or a truncated p53 (Delta121) did not activate the reporters containing p53 responsive elements from p21waf1, BAX, MDM2, p53AIP1, and PUMA genes at all. However, a mutant-p53 (Asn30Ser) showed the transcriptional activity on all of the reporters as wild-type p53 did. On the other hand, a mutant-p53 (Asp281His) activated the p21waf1 promoter strongly and the MDM2 promoter faintly, but did not activate the BAX promoter. Interestingly, this mutant-p53 prevented Saos-2 cells from undergoing apoptosis after treatment with a DNA damaging agent, adriamycin. This mutant-p53 induced cell cycle arrest but not apoptosis. Furthermore, another mutant-p53 (Glu17Lys, His193Leu) also prevented the cells from undergoing apoptosis after DNA damage probably in a transcription-independent manner. These results suggest that some cancer cells may contain the oncogenic mutation of the p53 gene, and the oncogenic p53 protein prevents cancer cells from undergoing apoptosis after DNA damage. Detailed information for mutated p53 gene in cancer cells might provide useful suggestions for the therapeutic strategy.


Subject(s)
Apoptosis , DNA Damage , Genes, p53 , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Mutation , Base Sequence , Blotting, Western , Cell Line , Cell Line, Tumor , Cell Survival , DNA, Complementary/metabolism , Humans , Molecular Sequence Data , Open Reading Frames , Tumor Suppressor Protein p53/chemistry
5.
Curr Pharm Des ; 12(3): 379-85, 2006.
Article in English | MEDLINE | ID: mdl-16454751

ABSTRACT

Treating malignant tumor through the induction of cell differentiation has been an attractive concept, but clinical development of differentiation-inducing agents to treat malignant tumor, especially for solid tumors has been limited to date. Nerve growth factor, all trans retinoic acid, dimethyl sulfoxide, active form vitamin D(3), peroxisome proliferator-activated receptorgamma, 12-0-tetradecanoylphorbol 13-acetate, hexamethylene-bis-acetamide, transforming growth factor-beta, butyric acid, cAMP, and vesnarinone are known to have a differentiation-inducing capability on solid tumors in vitro and/or in vivo. Moreover some of the differentiation-inducing agents have been used for treating patients with solid tumor, but the therapeutic effect of the differentiation-inducing agents on solid tumor is not strong when compared with that of conventional chemotherapeutic agents. However, because most of the differentiation-inducing agents can potentiate the effect of conventional chemotherapy or radiation therapy, combination of differentiation-inducing therapy with conventional chemotherapy or radiation therapy might be used as a second- or third-line therapy in patients with advanced cancer. Furthermore, analysis of the molecular mechanisms of the tumor differentiation therapy might provide selective and targeted molecules for novel cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Differentiation/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Animals , Humans , PPAR gamma/pharmacology , Pyrazines , Quinolines/pharmacology
6.
Hepatogastroenterology ; 52(61): 264-9, 2005.
Article in English | MEDLINE | ID: mdl-15783046

ABSTRACT

We report 2 cases of ruptured pancreaticoduodenal artery aneurysm (PDAA) treated by transcatheter embolization (TAE). In the first case, a 63-year-old man complained of sudden abdominal pain and was transferred to our hospital because he collapsed in a state of shock. Abdominal computed tomography (CT) revealed retroperitoneal hematoma and ascites. Abdominal angiography showed bleeding from one of the branches of the inferior pancreaticoduodenal artery. The ruptured PDAA was terminated by TAE. In the second case, a 65-year-old man experienced sudden abdominal pain. Abdominal CT revealed a retroperitoneal hematoma. He received TAE to terminate bleeding from a PDAA, but his abdominal pain worsened. At operation, ileus caused by the hematoma compressing the transverse colon was diagnosed, and cecostomy was performed. He recovered well and was discharged a few days later. In summary, a patient with a ruptured PDAA should first be treated by TAE, followed if necessary by surgery.


Subject(s)
Aneurysm, Ruptured/therapy , Duodenum/blood supply , Embolization, Therapeutic , Pancreas/blood supply , Aged , Aneurysm, Ruptured/diagnostic imaging , Catheterization , Duodenum/diagnostic imaging , Humans , Male , Middle Aged , Pancreas/diagnostic imaging , Radiography
7.
J Gastrointest Surg ; 9(4): 498-502, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15797230

ABSTRACT

A 59-year-old woman underwent surgery for uterine corpus cancer in March 1998. She also underwent pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy for common bile duct cancer in November 1998. She was followed up at our outpatient clinic after pylorus-preserving pancreaticoduodenectomy. In November 2002, her carcinoembryonic antigen level became elevated and abdominal ultrasound revealed a huge tumor. Gastroscopy showed a Borrmann type 3 tumor at the anastomosis of the pancreaticogastrostomy, and a biopsy revealed adenocarcinoma. With a diagnosis of advanced gastric cancer, she underwent total gastrectomy, splenectomy, and residual pancreatectomy in January 2003. The pathologic findings revealed that the gastric cancer was separated from the pancreas, suggesting that the cancer had developed from the stomach. The present report describes a rare case of gastric cancer that had developed at the anastomosis of a pancreaticogastrostomy.


Subject(s)
Adenocarcinoma/secondary , Common Bile Duct Neoplasms/pathology , Stomach Neoplasms/secondary , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Common Bile Duct Neoplasms/surgery , Female , Gastrectomy , Gastroscopy , Humans , Pancreaticoduodenectomy , Splenectomy , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
8.
Int J Oncol ; 25(4): 913-20, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15375540

ABSTRACT

Mutations of p53 tumor suppressor gene increase with tumor progression in colorectal cancers. In this study, we examined the expressions of p33ING1, p14ARF, MDM2 and p21WAF1 mRNA in 25 advanced colorectal cancers by quantitative RT-PCR method, and compared the expression levels of p33ING1, p14ARF, p21WAF1 and MDM2 in relation to p53 status in the tumors. Fifteen of 25 colorectal cancers (60%) showed abnormal accumulation of p53 protein in the nucleus, and the remaining 10 colorectal cancers (40%) were negative for p53 immunostaining. We found a G --> T transition (nonsense mutation) at the first nucleotide of codon 298 (exon 8) in one p53-negative case, and a frame shift mutation on exon 7 in another p53-negative case. In remaining eight p53-negative cases, there was no mutation in the entire open reading frame of p53 cDNA. Interestingly, in eight cases with p53 wild-type gene, 6 cases (75%) showed a marked down-regulation of p14ARF mRNA, and three cases (37.5%) over-expressed MDM2 mRNA. Only one case with wild-type p53 gene showed normal level expression of p53 regulatory-factors (p33ING1, p14ARF, and MDM2). Thus, p53 tumor suppressor pathway was disrupted in 24 of 25 colorectal cancers (96%).


Subject(s)
Cell Cycle Proteins/genetics , Colorectal Neoplasms/genetics , Genes, p53/physiology , Mutation , Nuclear Proteins/genetics , Proteins/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p14ARF/genetics , Aged , Aged, 80 and over , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21 , DNA-Binding Proteins , Female , Genes, Tumor Suppressor , Humans , Inhibitor of Growth Protein 1 , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Proto-Oncogene Proteins c-mdm2 , RNA, Messenger/analysis , Tumor Suppressor Proteins
9.
Anticancer Res ; 23(3C): 2891-6, 2003.
Article in English | MEDLINE | ID: mdl-12926130

ABSTRACT

We present a new approach towards the detection of the mRNAs in formalin-fixed, paraffin-embedded samples using a reverse transcriptase (RT)-polymerase chain reaction (PCR). The total RNAs were extracted from 10-micron-thick sections and were reverse-transcribed, then the RT-products were subjected to PCR amplification of GAPDH mRNA for screening the mRNA degradation. Next, nested PCR was performed for examining the expression of p53-related genes, p21WAF1, MDM2, p33ING1 and p14ARF. GAPDH mRNA expression was detectable in 12 out of 21 oral squamous cell carcinoma (SCC) samples. p21WAF1 mRNA expression was detectable in 5 out of 12 SCC samples, MDM2 mRNA expression was detectable in 5 our of 12 SCC samples and p33ING1 mRNA expression was detectable in 6 out of 12 SCC samples. However, the expression of p14ARF mRNA was not detectable in any of the samples. Seven out of 12 oral SCC samples showed abnormal nuclear accumulation of p53 protein by immunohistochemical staining, whereas 5 out of 12 oral SCCs showed negative staining for p53 protein. Of of p33ING1 mRNA. One of these was a verrucous carcinoma in which the p53 gene products might be inactivated by the oncoprotein E6 of human papilloma virus. Thus, the p53 tumor suppressor pathway was disrupted in most oral SCCs at the cellular levels, due to either an abnormality in p53 itself or loss of expression of p53 regulatory factors. This method would assist in making diagnosis, determining therapeutic strategy and predicting the prognosis of various cancers including oral SCCs.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/genetics , Nuclear Proteins , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53/genetics , Animals , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Cycle Proteins , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/biosynthesis , Cyclins/genetics , DNA-Binding Proteins , Formaldehyde , Genes, Tumor Suppressor , Glyceraldehyde-3-Phosphate Dehydrogenases/biosynthesis , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Humans , Immunohistochemistry , Inhibitor of Growth Protein 1 , Intracellular Signaling Peptides and Proteins , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Paraffin Embedding , Protein Biosynthesis , Proteins/genetics , Proto-Oncogene Proteins/biosynthesis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-mdm2 , RNA, Messenger/biosynthesis , Tissue Fixation , Tumor Suppressor Protein p14ARF/biosynthesis , Tumor Suppressor Protein p14ARF/genetics , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Proteins
10.
Cancer Sci ; 94(8): 699-706, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12901795

ABSTRACT

We isolated a metastasizing human esophageal squamous cell carcinoma (SCC) cell line, T.Tn-AT1, from a parental non-metastasizing cell line, T.Tn, by in vitro selection and by use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in T.Tn-AT1 and T.Tn by cDNA microarray analysis. The gene expression profiles of T.Tn and T.Tn-AT1 were very similar, and only 34 genes showed more than 3-fold differential expression. Among the 34 genes, 29 genes were down-regulated and only 5 genes were up-regulated in T.Tn-AT1 cells. Subsequently, we confirmed the expression levels of 14 of the 34 genes in T.Tn and T.Tn-AT1 cells by means of reverse transcription-polymerase chain reaction. The expression of 8 genes (KAL1, HPGD, NDN, REG1A, CXCR4, SPOCK, DIAPH2 and AIF1) was down-regulated and that of one gene (VNN2) was up-regulated in T.Tn-AT1 cells. These 9 genes encoded proteins associated with metastatic processes, such as adhesion, migration, inflammation, proliferation, and differentiation. Thus, these genes might regulate the metastasis of esophageal SCC, and could be predictive markers for lymph node metastasis of esophageal SCC.


Subject(s)
Esophageal Neoplasms/genetics , Oligonucleotide Array Sequence Analysis/methods , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Clone Cells , DNA Primers , DNA, Neoplasm/chemistry , DNA, Neoplasm/genetics , Esophageal Neoplasms/pathology , Gene Expression Profiling/methods , Humans , Neoplasm Metastasis/genetics , Tumor Cells, Cultured
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