It is not yet understood how the enhanced expression of pancreatic adenocarcinoma up-regulated factor (PAUF; a novel oncogene identified in our recent studies), contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up-regulates the expression and transcriptional activity of beta-catenin while the suppression of PAUF by shRNA down-regulates beta-catenin. The induction of beta-catenin by PAUF is mediated by the activities of Akt and GSK-3beta, but inhibition of downstream ERK does not reduce beta-catenin expression. To test whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated signaling pathway for the stabilization of beta-catenin, we examined the phosphorylation status of beta-catenin in the presence of PAUF compared with that of beta-catenin during treatment with Wnt3a or dibutyryl cAMP, a cell permeable cyclic AMP analogue. PAUF expression induces phosphorylation at Ser-33/37/Thr-41 and Ser-675 of beta-catenin but no phosphorylation at Ser-45, indicating that a unique phosphorylation pattern of beta-catenin is caused by PAUF. Finally, the expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of beta-catenin, leading to a rapid proliferation of pancreatic cells; conversely decreased PAUF expression (by shRNA) results in the reduced proliferation of pancreatic cells. Treatment with hexachlorophene (an inhibitor of beta-catenin) reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken together, we propose that PAUF can up-regulate and stabilize beta-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells.
*Adenocarcinoma/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/metabolism ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3/metabolism ; HEK293 Cells ; Humans ; Lectins/genetics/*metabolism ; *Pancreatic Neoplasms/metabolism/pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Signal Transduction ; *Up-Regulation ; beta Catenin/genetics/*metabolism

Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.
Astrocytoma ; genetics ; metabolism ; pathology ; Cell Adhesion Molecules ; genetics ; metabolism ; Cell Line, Tumor ; Central Nervous System Neoplasms ; genetics ; metabolism ; pathology ; CpG Islands ; genetics ; DNA Methylation ; Down-Regulation ; Gene Deletion ; Glioblastoma ; genetics ; metabolism ; pathology ; Humans ; Oligodendroglioma ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; Survival Rate

OBJECTIVESince human mast cell is an important source of cytokines, it is of importance to understand the effects of anti-allergic drugs on cytokines modulation in mast cells. In the present study, we aimed at observing whether IL-4 could be released from human mast cell line (HMC-1) after the stimulation of PMA + A23187, and the effects of systemic glucocorticosteroid, dexamethasone, topical glucocorticosteroid, budesonide and H1 antagonist, desloratadine on IL-4 release and mRNA expression.

METHODSHMC-1 was stimulated with 25 ng/ml phorbol 12-myristate 13-acetate (PMA) and 2.5 x 10(-7) mol/L ionomycin (A23187) and cultured for 6 hours, 12 hours and 24 hours respectively in the presence or absence of 10(-6)-10(-10) mol/L concentrations of test drugs. Culture supernatants were collected and the levels of IL-4 were assayed by enzyme-linked immunosorbent assays (ELISA). The mRNA expression of IL-4 was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSHMC-1 expressed IL-4 mRNA and the resulting protein production of IL-4 released after being stimulated with PMA plus A23187. Dexamethasone, budesonide and desloratadine had potent inhibitory effect on IL-4 release at any concentrations and time points, with significant deference (P < 0.05) compared to the control cells. The inhibitory effect did not show time-dependent and concentration-dependent manner. Desloratadine and budesonide showed neither up-regulatory nor down-regulatory effects on IL-4 mRNA expression at the test concentrations, however, desloratadine could down-regulate IL-4 mRNA expression.

CONCLUSIONSHMC-1 could express and produce IL4 after stimulation. Dexamethasone, budesonide and desloratadine all had inhibitory effects on IL-4 release from HMC-1. In addition, desloratadine could also inhibit the IL-4 mRNA expression.

Budesonide ; pharmacology ; Cell Line ; Dexamethasone ; pharmacology ; Humans ; Interleukin-4 ; biosynthesis ; Loratadine ; analogs & derivatives ; pharmacology ; Mast Cells ; drug effects ; metabolism ; Tetradecanoylphorbol Acetate ; pharmacology

OBJECTIVES: To evaluate the intra- and post-operative risks of myomectomies during cesarean section. MATERIALS AND METHODS: This study is a retrospective review of myomectomy during cesarean section performed from January 1, 1998, to December 31, 2000, at the Department of Obstetrics and Gynecology, School of Medicine, Pochon CHA University, Seoul, Korea. The subjects were 88 pregnant women diagnosed with leiomyoma. The outcome measures were hemoglobin drop, blood loss, need for blood transfusion, intra- and post- operative complications. RESULTS: The mean age of the patients was 32.5 +/- 4.4 and nulliparas(84.1%) were prevalent. The mean gestational age was 38 +/- 1.19 wks. Single myoma was found in 67% of cases, 50% located in the uterine corpus and 50% of cases were subserosal. type. The mean blood loss was 731.5 +/- 238ml range 400-2500. Twelve patients(13.6%) had blood transfusion. There was one case of re-operation because of post-operative bleeding. But there was no case of severe hemorrhage necessitating hystrectomy. CONCLUSION: Myomectomy during cesarean section is not such a hazardous procedure as many now believe.
Blood Transfusion ; Cesarean Section* ; Female ; Gestational Age ; Gynecology ; Hemorrhage ; Humans ; Korea ; Leiomyoma ; Methods ; Myoma ; Obstetrics ; Outcome Assessment (Health Care) ; Pregnancy ; Pregnant Women ; Retrospective Studies ; Seoul

To report cases of metastasectomy for metastatic gynecologic malignancies, we reviewed the medical records of all patients who have undergone metastasectomy for metastatic gynecologic malignancies in Center for Uterine Cancer from June 2001 to October 2002. Six patients were identified with median age of 55 years (range 52-66 years). The metastatic sites and primary sites were as follows: 3 liver metastasis from ovary; 1 abdominal wall metastasis from uterus (endometrial cancer), 1 brain metastasis from ovary, 1 lung metastasis from uterus (sarcoma). The median disease free interval was 48 months (range 10 months-13 years). There was no perioperative mortality. Postoperative morbidity was tolerable with 1 case of bile leakage. In three patients with hepatectomy, one patient was dead of disease after 15 months, one patient is alive with disease at 20 months of follow up, one patient have no evidence of recurrence at 7 months follow up. The patient with brain metastasis was dead due to lung metastsis after 9 months later postoperatively. Remaining two patients with abdominal wall and lung metastasis have no evidence of tumor recurrence at 4, 7 months follow up respectively. Metastasectomy for metastatic gynecologic malignancies can be performed safely and may help prolong survival in carefully selected patients.
Abdominal Wall ; Bile ; Brain ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver ; Lung ; Medical Records ; Metastasectomy ; Mortality ; Neoplasm Metastasis ; Ovary ; Recurrence ; Uterine Neoplasms ; Uterus

OBJECTIVE: To characterize the clinical features of platinum compounds (cisplatin plus carboplatin) associated hypersensitivity reactions. METHODS: Medical records of 102 patients with gynecologic malignancy who received chemotherapy based on platinum at Center for Uterine Cancer from Jun. 2001 to Nov. 2002 were analyzed. Platinum hypersensitivity reaction was classified as acute and delayed reaction according to the time of onset, also mild and severe reaction according to the severity of symptoms and signs. RESULTS: Among the 102 patients treated with platinum compounds during this period, 20 (20%) developed hypersensitivity reaction. The median number of platinum courses for the first episode was 7 (range 4-9) and it concentrated at 7, 8, 9th cycles. Fourteen patients developed acute reaction and six patients experienced delayed reaction. Ten patients experienced severe symptoms including dyspnea. Acute reaction developed from a few minutes to 30 minutes after the initiation of the platinum infusion. Delayed reaction developed after discharge of patients with mild intensity. CONCLUSION: Platinum hypersensitivity reactions develop in patients who have been extensively pre- treated with these agents. As platinum compounds are increasingly used as neoadjuvant, initial, second-line chemotherapy of ovarian cancer and concurrent chemoradiation, palliative setting of cervical cancer, it can be anticipated that hypersensitivity reactions to these drugs will happen more frequently, at the same time it might be a important issue for clinicians engaged in chemotherapy.
Carboplatin* ; Cisplatin* ; Drug Therapy ; Dyspnea ; Humans ; Hypersensitivity* ; Medical Records ; Ovarian Neoplasms ; Platinum ; Platinum Compounds ; Uterine Cervical Neoplasms ; Uterine Neoplasms

OBJECTIVE: The purpose of this study was to investigate the clinical feasibility of FDG-PET scan in selection of patients with pelvic recurrence of cervical cancer for surgical treatment. METHODS: From Jun. 2001 to Oct. 2002, whole body FDG-PET scan findings were compared with findings of CT, MRI, and pathologic reports in 24 patients with pelvic recurrence of cervical cancer. PET scan was obtained with a GE Advance PET scanner, beginning at 60 minutes after injection of 370-555 MBq (10- 15 mCi) of 18F FDG. Regional scan was also obtained if needed. Uptake exceeding 2.5 SUV was determined as a positive finding. RESULTS: Among these 24 patients, 10 patients had metastatic lesions at pelvic lymphnodes (4), para- aortic lymphnodes (3), mediastinal lympnnodes (1), lung (4), and bone (1). Among 14 patients with no metastasis, 10 patients underwent surgical treatment but the operations were abandoned in 2 patients due to lymphnodes metastasis and pelvic peritoneal spreads that confused as normal FDG uptake of the intestines pre- operatively. Among 8 patients whom the operation was completed, 3 patients received pelvic exenteration, 2 patients received CORT, and 3 patients received LEER. CONCLUSION: FDG-PET is clinically feasible in selection of patients with pelvic recurrence of cervical cancer for surgical treatment.
Humans ; Intestines ; Lung ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Pelvic Exenteration ; Positron-Emission Tomography ; Recurrence* ; Uterine Cervical Neoplasms*

OBJECTIVETo study the effects of wild-type PTEN on gene expressions of glioblastomas.

METHODSGlioblastoma U87MG cells, which express inactivated PTEN, were transfected with wild-type PTEN constructs and stable transfected clones were selected. Then, cDNA microarray analyses were used to identify differentially expressed genes in wild-type PTEN transfected cells and control cells.

RESULTSTransfected wild-type PTEN inhibited the proliferation of U87MG. By cDNA microarray analyses, 89 cDNA clones were identified, which were differentially expressed in wild-type PTEN transfected cells and control cells. Among these genes, 13 genes were unknown and 76 genes were known genes, including glial fibrillary acidic protein, p21/WAF1, human TGF-beta inducible early protein, human DNA fragmentation factor 45 etc.

CONCLUSIONWild-type PTEN can affect the expressions of multiple genes, by which it regulates the proliferation, differentiation and apoptosis of glioblastomas.

Brain Neoplasms ; genetics ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Glioblastoma ; genetics ; Humans ; Oligonucleotide Array Sequence Analysis ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases ; genetics ; physiology ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Proteins ; genetics ; physiology

5% of ovarian neoplasms consist of granulosa cell tumors. 10% of cases coexist with pregnancy2. We report on delivery of normal infant in young woman with granulosa cell tumor diagnosed and treated during pregnancy. At laparotomy a large right ovarian granulosa cell tumor was found and right salpingo- oophorectomy was performed. A normal infant was delivered by cesarean section at full term.
Cesarean Section ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Infant ; Laparotomy ; Ovarian Neoplasms ; Ovariectomy ; Ovary* ; Pregnancy*

OBJECTIVE: The object of this study was to assess the accuracy of dipyridamole stress intravenous (IV) myocardial contrast echocardiography (MCE) using pulse inversion harmonic imaging and PESDA in the detection of perfusion defect in the patients with coronary artery disease in comparison with dipyridamole stress Tc-99m sestamibi SPECT. METHODS: Total 46 patients (29 males, mean age 64 years old) were consecutively enrolled. Patients with prior myocardial infarction were excluded. MCE and Tc-99m sestamibi SPECT were performed at the same day during rest and after 0.56 or 0.84mg/Kg dipyridamole infusion. Continuous IV infusion of PESDA (2-5 mL/min) was administered while obtaining triggered (1:1) end-systolic apical 2, 4 chamber and long axis views. Tc-99m sestamibi was injected 3 minutes after dipyridamole. Tc-99m sestamibi SPECT images were obtained one hour later. Coronary angiography was followed within two days in all patients. Tc-99m sestamibi SPECT images were matched to the sixteen segments of left ventricle according to American Society of Echocardiography for segmental comparison. Both images were analyzed visually. Results Using coronary angiography as the standard, MCE showed overall sensitivity of 70.7%, specificity of 95.8%, positive predictive value (PPV) of 87.8% and negative predictive value (NPV) of 88.5% in the detection of coronary atherosclerosis (70% stenosis). Tc-99m sestamibi SPECT showed sensitivity of 75.6%, specificity of 98.9%, PPV of 96.8% and NPV of 90.6%. The overall concordance rate between MCE and Tc-99m sestamibi SPECT for the detection of perfusion defects was 86.9% (Cohen's kappa value 0.63) according to the coronary territory and 86.8% (Cohen's kappa value 0.55) according to segmental analysis. CONCLUSION: Dipyridamole stress IV MCE using pulse inversion harmonic imaging and PESDA is feasible and comparable to Tc-99m sestamibi SPECT in identifying significant coronary stenosis and inducible myocardial perfusion defects in the patients with coronary artery disease. MCE using pulse inversion harmonic imaging seems to be a promising modality for assessing myocardial perfusion in the patients with suspected coronary artery disease.
Axis, Cervical Vertebra ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis ; Dipyridamole ; Echocardiography* ; Heart Ventricles ; Humans* ; Male ; Myocardial Infarction ; Perfusion* ; Sensitivity and Specificity ; Tomography, Emission-Computed, Single-Photon*