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Biomedical subjects

Sung-Soo Park

Publications and source records attributed to Sung-Soo Park.

17 recordsLinked to original sources

Gastric neuroendocrine carcinoma: clinicopathologic review and immunohistochemical study of E-cadherin and Ki-67 as prognostic markers.

BACKGROUND AND OBJECTIVES: Gastric neuroendocrine carcinoma (NEC) is an uncommon cancer of the stomach. The classification of NEC and its clinical behavior remains controversial, and prognostic markers and their therapeutic guidelines have not been clearly defined. The aim of this study was to evaluate the clinicopathologic characteristics of these tumors and analyze the expression of E-cadherin and Ki-67 as prognostic markers in gastric NECs. METHODS: We retrospectively reviewed 17 cases of gastric NECs. Tumor pathology was reviewed and the tumors were categorized as well-differentiated NEC (n = 5) and poorly differentiated NEC (n = 12) according to the WHO classification. With the aim of evaluating the expression of E-cadherin and Ki-67 and their prognostic role in gastric NEC, immunohistochemical analysis of the tumors was performed. RESULTS: The median survival of patients was 20.0 months (95% confidence interval (CI), 13.2-28.8). There was a statistically significant difference in overall survival between well and poorly differentiated NECs (P = 0.021). However, there was no significant difference in overall survival between patients with poorly differentiated small cell and large cell NEC (P = 0.796). Loss of E-cadherin was correlated with lymph node metastasis (P= 0.044). A high Ki-67 proliferation index (PI) (>60%) was correlated with tumor recurrence (P = 0.013) and histologic differentiation (P= 0.028). CONCLUSIONS: Loss of E-cadherin may predict lymph node metastasis in gastric NECs. A high Ki-67 PI (>60%) could be used as a prognostic marker to predict aggressive gastric NECs in addition to standard pathologic classification.

Aged↗

Reversal of drug resistance in breast cancer cells by transglutaminase 2 inhibition and nuclear factor-kappaB inactivation.

Induction of transglutaminase 2 (TGase 2) by epidermal growth factor (EGF) in human breast cancer cells increases their oncogenic potential and chemoresistance. The role of TGase 2 in the development of these tumor-related phenotypes remains to be elucidated, but it has been shown that expression of a dominant-negative form of TGase 2 reverses EGF-mediated chemoresistance in breast cancer cells. We examined several different breast cancer cell lines, representing both EGF receptor (EGFR)-positive and EGFR-negative breast cancers, and found that doxorubicin-resistant cells had a higher level of TGase 2 compared with doxorubicin-sensitive cells independent of the EGFR expression level. TGase 2 inhibition increased the chemosensitivity of drug-resistant cells, concomitant with a decrease in nuclear factor-kappaB (NF-kappaB) activity. Increasing the level of TGase 2 in drug-sensitive cells by transient transfection reduced the level of inhibitory subunit alpha of NF-kappaB (IkappaBalpha) and increased NF-kappaB activity in these cells. Inhibition of TGase 2 in drug-resistant cells by RNA interference increased the levels of IkappaBalpha, and this correlated with a shift in the accumulation of NF-kappaB from the nucleus to the cytosol. We recently showed that TGase 2 activated NF-kappaB through polymerization and depletion of free IkappaBalpha during inflammation. Therefore, increased expression of TGase 2 and subsequent activation of NF-kappaB may contribute to drug resistance in breast cancer cells independently of EGF signaling.

Apoptosis↗

Expression of liver-intestine cadherin and its correlation with lymph node metastasis in gastric cancer: can it predict N stage preoperatively?

BACKGROUND: Reliable method to predict lymph node metastasis is not yet available. In the present study, therefore, we examined LI-cadherin expression in human gastric cancer and attempted to find its relationship with clinicopathologic data, especially with lymph node metastasis. We also analyzed the expression in preoperative biopsy specimen to uncover its possibility of prognostication for lymph node metastasis. METHODS: The paired preoperative endoscopic biopsy and postoperative resected specimens from 208 patients who had surgically been treated for gastric cancer were retrospectively analyzed immunohistochemically for expression of LI-cadherin. RESULTS: There were 47 (22.6%) and 161 (77.4%) tumors which had positive and negative LI-cadherin expression, respectively. LI-cadherin expression was significantly correlated with tumor histology and lymph node metastasis: Furthermore, reduced expression of LI-cadherin was closely associated with tumor progression and lymph node metastasis in human gastric carcinoma. LI-cadherin expressions in both resected tumor and preoperative endoscopic tissues were found to be independent factors associated with lymph node metastasis. CONCLUSIONS: There is a close association between reduced expression of LI-cadherin and lymph node metastasis in human gastric cancer. Immunohistochemical study of LI-cadherin is relatively simple compared to sentinel node navigation surgery, and it could be a practical prediction method for lymph node metastasis in patients with this malignancy.

Biomarkers, Tumor↗

Transglutaminase 2 mediates polymer formation of I-kappaBalpha through C-terminal glutamine cluster.

Recently we reported that transglutaminase 2 (TGase 2) activates nuclear factor-kappaB (NF-kappaB) independently of I-kappaB kinase (IKK) activation, by inducing cross-linking and protein polymer formation of inhibitor of nuclear factor-kappaBalpha (I-kappaBalpha). TGase 2 catalyzes covalent isopeptide bond formation between the peptide bound-glutamine and the lysine residues. Using matrix-assisted laser desorption ionization time-of-flight mass spectra analysis of I-kappaBalpha polymers cross-linked by TGase 2, as well as synthetic peptides in an in vitro competition assay, we identified a glutamine cluster at the C terminus of I-kappaBalpha (amino acids 266-268) that appeared to play a key role in the formation of I-kappaBalpha polymers. Although there appeared to be no requirement for specific lysine residues, we found a considerably higher preference for the use of lysine residues at positions 21, 22, and 177 in TGase 2-mediated cross-linking of I-kappaBalpha. We demonstrated that synthetic peptides encompassing the glutamine cluster at amino acid positions 266-268 reversed I-kappaBalpha polymerization in vitro. Furthermore, the depletion of free I-kappaBalpha in EcR/TG cells was completely rescued in vivo by transfection of mutant I-kappaBalphas in glutamine sites (Q266G, Q267G, and Q313G) as well as in a lysine site (K177G). These findings provide additional clues into the mechanism by which TGase 2 contributes to the inflammatory process via activation of NF-kappaB.

Amino Acid Sequence↗

Prognostic factors for patients with node-negative gastric cancer: Can extended lymph node dissection have a survival benefit?

BACKGROUND AND OBJECTIVES: For the patients with node-negative gastric cancer, there is no agreement on which clinicopathological factors influence the final results except T stage. The aim of this study was to investigate the prognostic factors, and to reveal whether the extent of lymph node dissection is associated with survival benefit for these patients. METHODS: Clinicopathological data of 506 patients with node-negative gastric cancer were studied. We divided the patients into D1 and D2 groups and carried out univariate and multivariate survival analyses. RESULTS: On the univariate analysis, the factors influencing survival were age, tumor size, Borrmann type, resection type, and the T stage. However, multivariate analysis with the Cox proportional hazard model disclosed age and the T stage to be significant variables. The extent of lymphadenectomy was revealed to be the independent prognostic factors for survival only for the patients with T3 stage. CONCLUSIONS: For the patients with clinically node-negative gastric cancer, an extended D2 lymph node dissection for the patients with T1 and T2 stage has no survival benefits. Although it might have some benefit for T3 stage by multivariate analysis, we should ascertain its value through a large randomized prospective study.

Aged↗

Mouse disabled 2 interacting protein 2 functions as a transcriptional repressor through direct binding onto its own promoter.

The mDaIP2 protein is a mouse orthologue of human Nostrin (a regulator of eNos). The absence of eNos activity in RA-treated F9 cell implies that the protein plays somehow different role from Nostrin. In this experiment, this protein has been shown to repress the expression of its own gene, via a feedback mechanism which involves binding to the promoter region. Data from cotransfection, DNAP, mDaIP2-silenced F9 cell, and EMSA analyses clearly support the repression activity and direct binding of the protein to the promoter region. The protein contains N-terminal FCH domain and C-terminal SH3 domain. The SH3 domain is known to interact with the proline-rich domain of mDab2, while even no function has been reported about the FCH domain. Here, we report a novel function of mDaIP2 as a transcriptional repressor and suggest the possible association of the FCH domain with transcriptional regulation.

5' Flanking Region↗

Mesenteric Castleman's disease.

We report here a rare case of mesenteric Castleman's disease presenting as a mesenteric mass. A 13-year-old female child was admitted to our hospital complaining of intermittent vague abdominal pain. She had hypochromic anemia, thrombocytosis and an elevated erythrocyte sedimentation rate (ESR). Ultrasonography and computed tomography indicated an intra- abdominal mass might represent a lymphoma or gastrointestinal stromal tumor or leiomyoma, but the definitive preoperative diagnosis couldn't be confirmed. The surgical resection of the mass revealed the mesenteric hyaline vascular-type Castleman's disease.

Adolescent↗

Cloning and characterization of mouse disabled 2 interacting protein 2, a mouse orthologue of human NOSTRIN.

The mouse disabled 2 interacting protein 2 (mDaIP2) had been obtained through yeast two hybrid system. It consists of 506 amino acids and its calculated molecular weight is 57.7 kDa. The protein contains N-terminal FCH domain and C-terminal SH3 domain. The SH3 domain interacts with the proline rich domain of mDab2 which had been identified to possess a transcriptional activation function. In RA-treated F9 teratocarcinoma cell, the mDaIP2 and mDab2 genes were differentially expressed in a RA-responsive manner and both were detected to localize in cytoplasm and nucleus. Homology search of all NCBI sequences indicated that the amino acid sequence of mDaIP2 shares 82% identity with human NOSTRIN which controls activity, trafficking, and targeting of nitric oxide synthase (eNos). The eNos was not detected in RA-treated F9 cell. These results suggest that mDaIP2 somehow functions in a different fashion from NOSTRIN in F9 cell differentiation and that its function may be concerted with that of mDab2.

Adaptor Proteins, Signal Transducing↗

Microaffinity purification of proteins based on photolytic elution: toward an efficient microbead affinity chromatography on a chip.

A bead affinity chromatography system, which was based on the photolytic elution method, was integrated into a glass-silicon microchip to purify specific target proteins. CutiCore beads, which were coupled with a photo-cleavable ligand, such as biotin and an RNA aptamer, were introduced into a filter chamber in the microchip. The protein mixture containing target protein labeled with fluorescein isothiocyanate (FITC) was then passed through the packed affinity beads in the microchamber by pressure-driven flow. During the process, the adsorbed protein on the bead was monitored by fluorescence. The concentrated target protein on the affinity bead was released by simple irradiation with UV light at a wavelength of 360 nm, and subsequently eluted with the phosphate buffer flow. The eluted target protein was quantitatively detected via the fluorescence intensity measurements at the downstream of the capillary connected to the outlet of the microchip. The microaffinity purification allowed for a successful method for the identification of specific target proteins from a protein mixture. In addition, the feasibility of this system for use as a diagnosis chip was demonstrated.

Biotin↗

Gastric cancer confined to the muscularis propria: a possible candidate for laparoscopic surgery or adjuvant therapy.

OBJECTIVE: Gastric cancer confined to the muscularis propria (mp) has a favorable prognosis, but still belongs to the advanced category. Many oncologists have difficulties in selecting treatment modalities owing to the confused situation of mp cancer. To clarify the therapeutic strategy, the clinicopathological characteristics were investigated, and the risk factors, of this intermediate-stage gastric cancer, evaluated. MATERIAL AND METHODS: A total of 155 patients who underwent curative resection for primary gastric cancer between 1993 and 2001 were diagnosed with mp cancer. The patients were divided into recurrent and non-recurrent groups and analyzed clinicopathologically. RESULTS: The rate of recurrence was 20%. A multivariate analysis disclosed only lymphatic metastasis as an independent risk factor for recurrence of mp cancer. Hematogenous metastasis accounted for 37% of the recurrent patterns, and the liver (83.3%) was the most common organ. The 5-year survival rate of all mp cancer patients was 80.9%, but that of patients with recurrent disease was 19.2%. The median survival time of the recurred patients was 24 months, and 74% of those patients died within 3 years. CONCLUSIONS: Lymph node metastasis is the only significant risk factor of mp cancer. Patients with lymphatic metastasis should undergo postoperative adjuvant therapy. On the other hand, patients with mp cancer without lymph node involvement have an excellent prognosis and could be candidates for laparoscopic gastric surgery.

Adenocarcinoma↗

Impact of skip metastasis in gastric cancer.

BACKGROUND: Several studies have shown the features of skip metastasis in other cancers besides gastric cancer. Since minimally invasive surgery has been applied to gastric cancer, the concerns and awareness of skip metastasis have grown in the medical community. We conducted the present retrospective study to reveal the clinicopathological characteristics of patients with skip metastasis. We also wished to clarify the clinical impact of skip metastasis for gastric cancer. METHODS: Five hundred and eighty-nine patients having lymphatic metastases were enrolled in the present study. Among them, 266 patients had positive nodes extending into the N2 group. We divided these patients into the skip positive (+) and the skip negative (-) group, and we comparatively analysed clinicopathological factors and calculated the survival probabilities for the two groups. RESULTS: The skip (+) and skip (-) groups involved 14 (5.3%) and 252 (94.7%) patients, respectively. Of all the investigated factors, a significant difference between two groups was observed only in the total number of retrieved nodes. Stations of skip nodes were along left gastric (7), anterior common hepatic (8a), celiac (9), splenic (11) artery and right paracardial nodes (1). The survival curves calculated in the present study did not show any statistical differences between the groups. CONCLUSIONS: Due to problems of skip metastasis in gastric cancer, D2 lymph node dissection should be performed until sentinel node detection is feasible and reliable. The potential risk from skip metastasis is not great and skip metastasis itself should not be a major consideration in therapeutic decisions.

Adenocarcinoma↗

Suppressive activity of protease inhibitors from buckwheat seeds against human T-acute lymphoblastic leukemia cell lines.

The buckwheat protease inhibitor designated BWI-1, a member of the potato inhibitor I family, inhibits trypsin, chymotrypsin, and subtilisin, whereas the buckwheat protease inhibitor designated BWI-2a, a novel protease inhibitor homologous to the vicilin family, inhibits only trypsin. We examined the suppressive activity of BWI-1 and BWI-2a against T-acute lymphoblastic leukemia (T-ALL) cells, such as JURKAT and CCRF-CEM, and human normal blood lymphocytes. Both inhibitors significantly suppressed the growth of T-ALL cells as judged by the soluble 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (tetrazolium/formazan assay). JURKAT cells showed slightly higher susceptibility to buckwheat inhibitors than CCRF-CEM cells. Modification of Arg residue(s) in inhibitors by 1,2-cyclohexandione inactivated their trypsin inhibitory activity, considerably abolishing their suppressive activity. This suggests that the trypsin inhibitory activity is involved in the suppression of growth of human T-ALL cell lines. It was further found that both inhibitors triggered programmed cell death (apoptosis) of these cell strains with DNA fragmentation.

Allergens↗

Integration of on-column immobilized enzyme reactor in microchip electrophoresis.

A simple method integrating an immobilized enzyme reactor into a microchip electrophoresis device was developed. The enzyme immobilization into a microchip was performed by spotting and drying a drop of dissolved nitrocellulose (NC) on a glass substrate, and adsorbing enzyme on the reconstituted NC membrane. This enzyme-immobilized glass plate was assembled with a polydimethylsiloxane substrate on which the separation channel was fabricated. The advantage of this method is the ability to easily change the position and size of the reactor within the microchip electrophoresis device. A beta-galactosidase reaction was demonstrated with fluorescein di-beta-D-galactopyranoside using this integrated on-column enzyme reactor. A successful electrophoretic separation of its hydrolysis products, i.e., fluorescein mono-beta-D-galactopyranoside (FMG) and fluorescein, was achieved. Enzyme kinetics and inhibition of the beta-galactosidase using FMG and 2-phenylethyl beta-D-thiogalactoside, respectively, were also studied with microchip electrophoresis.

Collodion↗

Protein patterning on silicon-based surface using background hydrophobic thin film.

A new and convenient protein patterning method on silicon-based surface was developed for protein array by spin coating of hydrophobic thin film (CYTOP). Photolithographic lift-off process was used to display two-dimensional patterns of spatially hydrophilic region. The background hydrophobic thin film was used to suppress nonspecific protein binding, and the hydrophilic target protein binding region was chemically modified to introduce aldehyde group after removal of the photoresist layer. The difference in surface energy between the hydrophilic pattern and background hydrophobic film would induce easier covalent binding of proteins onto defined hydrophilic areas having physical and chemical constraints. Below 1 microg/ml of total protein concentration, the CYTOP hydrophobic film effectively suppressed nonspecific binding of the protein. During the process of protein patterning, inherent property of the hydrophobic thin film was not changed judging from static and dynamic contact angle survey. Quantitative analysis of the protein binding was demonstrated by streptavidin-biotin system.

Biosensing Techniques↗