Biomedical subjects

Jin Sook Jeong

Publications and source records attributed to Jin Sook Jeong.

13 recordsLinked to original sources

PubMed2006

PKCtheta expression in gastrointestinal stromal tumor.

Gastrointestinal stromal tumor is characterized by a gain of function mutation of KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit expression is negative although histological findings of gastrointestinal stromal tumor are most suspicious. The existence of c-kit-negative gastrointestinal stromal tumors points to the need of additional markers for making the diagnosis. In this study, we studied the expression of PKCtheta and correlated their expression with other immunohistochemical profiles of gastrointestinal stromal tumors and evaluated their usability as a diagnostic marker. For this purpose, 220 gastrointestinal stromal tumors were immunohistochemically stained for PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c-kit-positive. PKCtheta was positive in 212 (96%) cases and c-kit was positive in 216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern. Out of 212 PKCtheta-positive GISTs, 208 (98%) cases were c-kit-positive, 174 (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100 protein was positive in 54 cases (26%). Genetic analyses on eight PKCtheta-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCtheta is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity.

Actins↗

PubMed2005

Detection of single nucleotide insertion of BCR/ABL region in imatinib-resistant human myelogenous leukemia SR-1 cells.

Imatinib mesylate is a selective Bcr/Abl kinase inhibitor and an effective anticancer agent for Bcr/Abl-positive chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Mutations within the BCR/ABL kinase domain are the most commonly identified mechanism associated with relapse. To overcome the imatinib resistance in CML, many investigators have tried to clarify molecular mechanism for imatinib resistance in cells of patients who failed to respond to imatinib. Our aim was to invesitigate underlying mechanism for imatinib resistance in SR-1 cells, which were derived from a CML patient in blast crisis. We detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression, which might be possible mechanism for the resistance to imatinib in SR-1 cells.

Amino Acid Sequence↗

PubMed2005

Specific regression of human cancer cells by ribozyme-mediated targeted replacement of tumor-specific transcript.

In this study, we describe a novel approach to human cancer therapy that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs with new transcripts that exert therapeutic activities. We have developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce transgene activity selectively in cancer cells that express the RNA. The ribozyme-mediated triggering of the transgene expression was accomplished via a high-fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. The ribozyme also induced cytotoxic activity in various hTERT-expressing cancer cells, hence selectively retarding the growth of those cells. Efficient and specific cell regression was also detected with ganciclovir (GCV) treatment only in hTERT-positive cancer cells, which were established to express stably the specific ribozyme that contains the herpes simplex virus thymidine kinase (HSV-tk) gene. Tissue-specific expression of the ribozyme could further augment the target specificity of the ribozyme. Importantly, we observed efficient regression of tumors with GCV treatment in mice that had been inoculated subcutaneously with hTERT-positive cancer cells that stably expressed the specific ribozyme that contains HSV-tk. These results suggest that the hTERT RNA-targeting trans-splicing ribozyme could be a powerful agent for tumor-targeted specific gene therapy.

Cytosine Deaminase↗

PubMed2005

Gastrointestinal stromal tumors in Koreans: it's incidence and the clinical, pathologic and immunohistochemical findings.

Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p = 0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p = 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.

Actins↗

PubMed2005

[A case of primary small cell carcinoma of the liver].

Primary small cell carcinoma of the liver is an extremely rare tumor. Extrapulmonary small cell carcinoma shares many features of pulmonary small cell carcinoma, including the histological appearance, the aggressive clinical behavior and the frequent short-lasting response to either chemotherapy or radiotherapy. We experienced a 56-year-old man with small cell carcinoma that arose in the liver. Abdominal CT scan showed an 8 cm size, low density mass in the segment 4 of the liver and also multiple lymphadenopathies. Chest X-ray showed no abnormal finding, but the chest CT showed a right lower paratracheal lymphadenopathy. The pathological findings showed nests of small round cells with fine granular chromatin, inconspicuous nucleoli and scanty cytoplasm. Distinct and strong immunoreactions were seen for CD56 and c-kit, and sparse immunoreaction was seen for synaptophysin. Thyroid transcription factor-1 showed no immunoreaction. The tumor did not decrease in size despite chemotherapy. We report this case along with a review of the relevant literatures.

Carcinoma, Small Cell↗

PubMed2004

Extrapulmonary small-cell carcinoma of the liver.

A 53-year-old man was admitted to our hospital for the evaluation of a mass (13 x 10 cm) in the left lobe of the liver seen by imaging studies. On subsequent biopsy of the mass, the lesion was histologically diagnosed as malignant small round-cell tumor, consistent with metastatic small-cell carcinoma. Segment IV segmentectomy was performed. On pathological examination, the mass showed a yellowish-gray granular appearance with multifocal hemorrhage and necrosis. The phenotypes shown by immunohistochemistry revealed characteristic patterns of small-cell carcinoma (neuron-specific enolase [NSE]+, synaptophysin+, c-Kit+, cluster designation [CD]56+, epithelial membrane antigen [EMA]+, cytokeratin [CK]7-). High resolution-computed tomography (HRCT) revealed inactive pulmonary tuberculosis with small calcified tuberculoma in the right upper lobe. Sputum cytology was negative for malignancy. The postoperative course was uneventful, and platinum-based chemotherapy (cisplatin, etoposide) was initiated.

Carcinoma, Small Cell↗

PubMed2004

Gene expression profiling of breast cancers with emphasis of beta-catenin regulation.

To gain molecular understanding of carcinogenesis of breast cancer, gene expression profiles were analyzed using cDNA microarray representing 4,600 cDNAs in 10 breast cancer samples and the adjacent noncancerous breast tissues from the same patients. The alterations in gene expression levels were confirmed by reversetranscription PCR in four randomly selected genes. Genes that were differently expressed in cancer and noncancerous tissues were identified. 106 (of which 55 were known) and 49 (of which 28 were known) genes were up- or down-regulated, respectively, in greater than 60% of the breast cancer samples. In cancer tissues, genes related to cell cycle, transcription, metabolism, cell structure/motility and signal transduction were mostly up-regulated. Furthermore, three cancer tissues showing immunohistochemically aberrant accumulation of beta-catenin in the nucleus and/or cytoplasm revealed down-regulation of Siah and Axin genes and up-regulation of Wnt and c-myc genes. These findings were highly consistent with Wnt signaling pathway associated with beta-catenin regulation previously suggested by others. Our studies, therefore, provide not only a molecular basis to understand biological processes of breast cancer but also useful resources to define the mechanism of beta-catenin expression in tumorigenesis of breast cancer.

Adult↗

PubMed2003

Hepatotoxin N-nitrosomorpholine-induced carcinogenesis in rat liver: ex vivo exploration of preneoplastic and neoplastic hepatocytes.

N-nitrosomorpholine (NNM) is a hepatotoxic and hepatocarcinogenic agent. This agent was administered in the form of drinking water which contained 200 mg of NNM/liter. Its time-dependent intake profile showed four phases over 20 weeks, followed by a fifth phase where only water was supplied. Most frequently, hepatocellular carcinoma appeared between the end of phase IV and the beginning of phase V. At 5 weeks of NNM administration, foci of altered hepatocytes (FAH) containing 100-1000 hepatocytes could be isolated together with free hepatocytes by the collagenase perfusion method. When these foci were grown on the William's Medium E containing hormonally defined medium, they were able to survive approximately twice as long as normal hepatocytes At 10 weeks of NNM administration, few FAH were isolated together with free hepatocytes. The hepatocytes which had been placed under extended chemical stress showed increased heat tolerance (7 to 8 h) at 43 degrees C, while normal hepatocytes could survive 3 to 4 h. At the neoplastic phase spanning the end of the 20 weeks of the NNM administration and water phase, the rats bearing hepatocellular carcinoma entered the terminal stage, where observable tumor masses could be isolated from the tumor bearing liver and tested for ex vivo growth in tissue culture. After stabilization of the isolated primary hepatoma cells through 10 passages of propagation on William's Medium E or minimal Eagle's medium containing 10% FBS, their gene expression profile was analyzed by DNA microarray and compared with the profile of normal hepatocytes. The comparison revealed that upregulation involved ribosome-dependent protein synthesis, including 40S ribosomal proteins (S4, S7, S18, S20), 60S ribosomal proteins (L6, L21, L32, L37, P1), initiation factor 4A, and elongation factor 1alpha.

Animals↗

PubMed2003

A gene expression in study human gastric adenocarcinoma using a cDNA microarray.

BACKGROUND/AIMS: cDNA microarray provides a powerful alternative with an unprecedented view scope in monitoring gene expression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim was to explore the different gene expression patterns in early and advanced gastric cancer. METHODS: By using a cDNA microarray representing 4,608 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and the adjacent noncancerous gastric tissues. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription (RT) PCR. RESULTS: Genes that were differently expressed in cancer and noncancerous tissues were identified. Forty-four and 92 (26 and 43 of them were known, respectively) genes or cDNA were up- and down-regulated, respectively, in more than 80% of gastric adenocarcinoma samples. The semi-quantitative RT-PCR results were consistent with the microarray findings. To distinguish between early and advanced gastric cancers, we used a supervised learning classification approach. When we used 16 and 20 genes as predictors, the prediction was all yielded statistically significant. Moreover, when we used 9 genes, we could predict with the highest accuracy. CONCLUSIONS: These results may provide not only a new molecular basis for understanding biological properties of gastric adenocarcinoma, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Sentinel lymph node biopsy with 99mTC tin-colloid in patients with gastric carcinoma.

BACKGROUND/AIMS: The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion. The objective of this study was to determine the feasibility of SLN biopsy in patients with gastric cancer for assessment of lymph node status. METHODOLOGY: From November 2001 through to July 2002, SLN biopsy was performed in twenty-two consecutive patients whose preoperative imaging studies showed T2 or T1 and no lymph node metastasis. Three hours prior to each operation, 99mTc tin-colloid (2.0ml, 1.0mCi) was injected into the submucosa of gastric tumor via endoscope. After SLN biopsy had been performed using gamma probe (NEO2000 Gamma Detection System, Neoprobe CO, 1999, USA), all the patients underwent radical gastrectomy. The SLN was cut and immediately manipulated for frozen section, and processed to make paraffin block for H&E and immunohistochemistry (IHC) staining. RESULTS: On average, 1.8 (range 1-5) SLNs were identified per patient. The location of all SLNs was in the perigastric area. No skip metastases were found. SLNs were identified in 20 of the 22 patients (success rate, 90.9%). The sensitivity of the SLN status in the diagnosis of the lymph node status was 82.2% (5/6) and the specificity was 100.0% (14/14). The diagnostic accuracy according to SLN status was 95.0% (19 of 20). CONCLUSIONS: SLN biopsy using radioisotope in patients with gastric cancer was a technically feasible procedure and a minimally invasive approach in the assessment of the nodal status in each patient.

Adenocarcinoma↗

PubMed2002

Changes in expression of cell cycle regulators after G1 progression upon repetitive thioacetamide treatment in rat liver.

Repetitive low dose thioacetamide (TA) treatment of hepatocytes was found to induce cells in G2 arrest. In the present study, an attempt was made to investigate alterations in expression of cell cycle regulators after G1 progression in the same repetitive low dose TA treated hepatocytes system and to define the determinators involved in G2 arrest. TA was daily administered intraperitoneally, with a dose of 50 mg/kg for 7 days. Expression levels of cyclin E and CDK2 were similar, increased at day 1 and reached a peak at day 2. And they recycled from day 3 reaching a second peak at day 5. Expression level of cyclin A was similar to p27(Kip1) and p57(Kip2) but not to CDK2 and increased to a peak level at day 2. Expression levels of cyclin B1 and cdc2 were similar although the cyclin B1 level was generally low, decreased from day 1 to basal levels at day 3 and persisted at a low level till day 7. The expression level of cyclin G1 was similar to p53 that peaked at day 3 and again at day 6 elevated over basal level. BrdU-labeled hepatocytic nuclei increased from 12 h, reached a peak at day 2, then decreased, and were not detectable from day 6. The number of PCNA-labeled nuclei increased immediately, peaked at day 2, and maintained till day 7. These results suggest that G2 arrest induced by repeated TA treatment might be p53-dependent, via activation of cyclin G1, rather than inhibition of cyclin B1- cdc2 complex, and inhibitors holding S phase progression might be p27(Kip1) and p57(Kip2).

Animals↗

PubMedDate not supplied

Hepatopulmonary syndrome induced by common bile duct ligation in a rabbit model: correlation between pulmonary vascular dilatation on thin-section CT and angiography and serum nitrite concentration or endothelial nitric oxide synthase (eNOS)1 expression.

OBJECTIVE: To investigate the correlation between radiologic vascular dilatation and serum nitrite concentration and eNOS expression in the endothelial cell and pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile duct ligation (CBDL). MATERIALS AND METHODS: Thin-section CT scans of the lung and pulmonary angiography were obtained 3 weeks after CBDL (n = 6), or a sham operation (n = 4), and intrapulmonary vasodilatation was assessed. The diameter and tortuosity of peripheral vessels in the right lower lobe by thin-section CT and angiography at the same level of the right lower lobe in all subjects were correlated to serum nitrite concentration and eNOS (endothelial nitric oxide synthase) expression as determined by immunostaining. RESULTS: The diameters of pulmonary vessels on thin-section CT were well correlated with nitrite concentrations in serum (r = 0.92, p < 0.001). Dilated pulmonary vessels were significantly correlated with an increased eNOS expression (r = 0.94, p < 0.0001), and the severity of pulmonary vessel tortuosity was found to be well correlated with serum nitrite concentration (r = 0.90, p < 0.001). CONCLUSION: The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD was dilated on thin-section CT and on angiographs. Our findings suggest that peripheral pulmonary vascular dilatations are correlated with serum nitrite concentrations and pulmonary eNOS expression.

Angiography↗

PubMedDate not supplied

Diagnostic utility of GLUT1 in the differential diagnosis of liver carcinomas.

BACKGROUND/AIMS: Malignant cells require high energy via glycolytic generation of ATP for cell proliferation and survival. This process is thought to be mediated by glucose transporters (GLUTs). GLUT1 appears to be expressed aberrantly in many cancers. The liver is the main organ closely related to glycogen metabolism and it is thought that GLUT expression might be altered in the tumors arising in the liver. METHODOLOGY: We studied GLUT1 expression in 22 hepatocellular carcinomas (HCC) and 16 cholangiocarcinomas (CC) and compared it to the expression of hepatocyte specific antigen (HSA) and cytokeratin 19 (CK19) by immunohistochemical studies. RESULTS: In HCC, GLUT1 was expressed in 4.5% (1/22), HSA in 77.3% (17/22) and CK19 in none (0/22). In CC, GLUT1 was expressed in 81.3% (13/16), HSA in none (0/16) and CK19 in 100% (16/16). Interestingly, GLUT1 was not expressed in normal hepatocytes and bile duct epithelium around the tumor, whereas CK19 was expressed in normal bile ducts and tumor cells. CONCLUSIONS: These results indicate that GLUT1 might be related to development of bile duct carcinoma and its expression was a more reliable marker for detection of bile duct carcinoma than CK19. Additionally, GLUT1 might potentially be useful as a means of distinguishing CC from HCC.

Bile Duct Neoplasms↗