Biomedical subjects

Sung Kim

Publications and source records attributed to Sung Kim.

15 recordsLinked to original sources

PubMed2006

Health-related quality of life among disease-free stomach cancer survivors in Korea.

Previous studies about the quality of life (QOL) in stomach cancer survivors focused on selected clinical parameters and did not consider the broader implications for overall health and QOL. We evaluated the impact of demographic and treatment-related factors on the QOL of stomach cancer survivors. We asked 391 stage I-III stomach cancer survivors who had been disease-free for at least 1 year after surgery to complete a demographic questionnaire, the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, and its stomach module, QLQ-STO22.Survivors undergoing total gastrectomy reported greater eating restrictions than those undergoing subtotal gastrectomy. Receiving chemotherapy or radiotherapy did not significantly affect any QLQ-C30 or QLQ-STO22 scores. Role and emotional functioning improved with increasing age, and stomach-specific symptoms (pain, eating restrictions, and anxiety) lessened. Compared with female survivors, male survivors had better physical and role functioning. Smoking status was also a significant negative predictor of physical functioning and anxiety. Comorbidities and selected demographic characteristics had a greater effect than type of treatment on the QOL of post-operative stomach cancer patients.

Aged↗

PubMed2006

Association mapping with single-feature polymorphisms.

We develop methods for exploiting "single-feature polymorphism" data, generated by hybridizing genomic DNA to oligonucleotide expression arrays. Our methods enable the use of such data, which can be regarded as very high density, but imperfect, polymorphism data, for genomewide association or linkage disequilibrium mapping. We use a simulation-based power study to conclude that our methods should have good power for organisms like Arabidopsis thaliana, in which linkage disequilibrium is extensive, the reason being that the noisiness of single-feature polymorphism data is more than compensated for by their great number. Finally, we show how power depends on the accuracy with which single-feature polymorphisms are called.

Algorithms↗

PubMed2006

Development of oncolytic adenovirus armed with a fusion of soluble transforming growth factor-beta receptor II and human immunoglobulin Fc for breast cancer therapy.

We have developed an approach to cancer gene therapy in which the oncolytic effects of an adenoviral vector have been combined with selective expression of a soluble form of transforming growth factor (TGF)-beta receptor II fused with Fc (sTGFbetaRIIFc). We chose to use adenoviral dl01/07 mutant because it can replicate in all cancer cells regardless of their genetic defects. An oncolytic adenovirus expressing sTGFbetaRIIFc (Ad.sT- betaRFc) was constructed by homologous recombination. Infection of MDA-MB-231 and MCF-7 human breast cancer cells with Ad.sTbetaRFc produced sTGFbetaRIIFc, which was released into the media. The conditioned media containing sTGFbetaRIIFc could bind with TGF-beta 1 and inhibited TGF-beta-dependent transcription in target cells. Infection of MDA-MB-231, MCF-7, and 76NE human breast cancer cells with Ad.sTbetaRFc resulted in high levels of viral replication, comparable to that of a wild-type dl309 virus. Although some viral replication was observed in actively dividing normal human lung fibroblasts, there was no replication in nonproliferating normal cells. Direct injection of Ad.sTbetaRFc into MDA-MB-231 human breast xenograft tumors grown in nude mice resulted in a significant inhibition of tumor growth, causing tumor regression in more than 85% of the animals. These results indicate that it is possible to construct an oncolytic virus expressing sTGFbetaRIIFc in which both viral replication and transgene expression remain intact, and the recombinant adenovirus is oncolytic in a human tumor xenograft model. On the basis of these results we believe that it may be feasible to develop a cancer gene therapy approach using Ad.sTbetaRFc as an antitumor agent.

Adenoviridae↗

PubMed2006

Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine.

We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.

1,2-Dimethylhydrazine↗

PubMed2005

Genome-wide association mapping in Arabidopsis identifies previously known flowering time and pathogen resistance genes.

There is currently tremendous interest in the possibility of using genome-wide association mapping to identify genes responsible for natural variation, particularly for human disease susceptibility. The model plant Arabidopsis thaliana is in many ways an ideal candidate for such studies, because it is a highly selfing hermaphrodite. As a result, the species largely exists as a collection of naturally occurring inbred lines, or accessions, which can be genotyped once and phenotyped repeatedly. Furthermore, linkage disequilibrium in such a species will be much more extensive than in a comparable outcrossing species. We tested the feasibility of genome-wide association mapping in A. thaliana by searching for associations with flowering time and pathogen resistance in a sample of 95 accessions for which genome-wide polymorphism data were available. In spite of an extremely high rate of false positives due to population structure, we were able to identify known major genes for all phenotypes tested, thus demonstrating the potential of genome-wide association mapping in A. thaliana and other species with similar patterns of variation. The rate of false positives differed strongly between traits, with more clinal traits showing the highest rate. However, the false positive rates were always substantial regardless of the trait, highlighting the necessity of an appropriate genomic control in association studies.

Arabidopsis↗

PubMed2005

An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach.

PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. METHODS AND MATERIALS: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. RESULTS: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). CONCLUSION: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.

Adenocarcinoma↗

PubMed2005

The pattern of polymorphism in Arabidopsis thaliana.

We resequenced 876 short fragments in a sample of 96 individuals of Arabidopsis thaliana that included stock center accessions as well as a hierarchical sample from natural populations. Although A. thaliana is a selfing weed, the pattern of polymorphism in general agrees with what is expected for a widely distributed, sexually reproducing species. Linkage disequilibrium decays rapidly, within 50 kb. Variation is shared worldwide, although population structure and isolation by distance are evident. The data fail to fit standard neutral models in several ways. There is a genome-wide excess of rare alleles, at least partially due to selection. There is too much variation between genomic regions in the level of polymorphism. The local level of polymorphism is negatively correlated with gene density and positively correlated with segmental duplications. Because the data do not fit theoretical null distributions, attempts to infer natural selection from polymorphism data will require genome-wide surveys of polymorphism in order to identify anomalous regions. Despite this, our data support the utility of A. thaliana as a model for evolutionary functional genomics.

Arabidopsis↗

PubMed2005

Repair of medial orbital wall fracture: transcaruncular approach.

The aim of this paper is to demonstrate the safety and the use of the transcaruncular approach as a surgical technique for managing a medial wall fracture. This approach was used in 40 patients with a isolated medial or a combined medial and inferior orbital wall fracture between September 1998 and September 2002. A computed tomographic scan was taken before and after surgery. The ocular motility and enophthalmos were checked before and after surgery. The transcaruncular approach provided the appropriate surgical exposure in all cases. Patients were followed up for a mean of 9.4 months (range, 524 months) after repairing the orbital wall fracture. Hertel exophthalmometry showed that among the 40 patients; 24 patients showed no enophthalmos. The enophthalmos ranged from 0.51 mm in 14 patients and 1.5 mm enphthalmos was noted in 2 patients. A clinically significant enophthalmos =2 mm was not found postoperatively. Preoperatively, 12 patients (30%) had a diplopia in the primary position of the gaze and 26 patients (65%) had a diplopia within 30 degrees of the gaze. Postoperatively, all patients had an orthotropia in the primary position but 4 patients (10%) had a residual diplopia either on the lateral gaze (2 patients) or the upgaze (2 patients). There were 2 cases of an implant misplacement. The transcaruncular approach provides a safe, rapid, and cosmetically pleasing surgical approach for managing a isolated medial wall fracture. When combined with the inferior transconjunctival approach, a combined medial and inferior orbital wall fracture can be successfully repaired.

Adolescent↗

PubMed2004

Effects of irradiated phytic acid on antioxidation and color stability in meat models.

Lipid oxidation and color stability of meats treated with irradiated phytic acid were investigated during storage for 2 weeks at 4 degrees C. The phytic acid in deionized distilled water (DDW) was degraded by irradiation at 10 and 20 kGy, and the irradiated phytic acid showed a strong antiradical activity. For measuring the antioxidant effects of irradiated phytic acid in food models, beef and pork were prepared with DDW (control), irradiated (10 and 20 kGy) or non-irradiated phytic acid, and ascorbic acid as a model system. Irradiated phytic acid significantly inhibited the lipid oxidation in meats compared to the control and ascorbic acid treated samples during storage (P < 0.05). The redness of the meats treated with phytic acid had a higher value than did the control and ascorbic acid treated samples, but a significant difference was not observed in the samples treated with phytic acid regardless of irradiation treatment. Irradiated phytic acid was also effective in inhibiting the loss of heme iron and metmyoglobin formation during storage. Results indicated that irradiation might be helpful for improving the antioxidant activity of phytic acid in meats.

Antioxidants↗

PubMed2004

Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells.

It is widely accepted that T helper type 1 (T(H)1) cytokines such as interferon-gamma (IFN-gamma) antagonize allergic diseases mediated by T(H)2 cytokines. The 'hygiene hypothesis' has also proposed that decreased childhood exposure to pathogen-derived T(H)1 cytokines may underlie the recent increased prevalence of asthma, a T(H)2-mediated disease. We show here that influenza A viral infection, which induces large amounts of intrapulmonary IFN-gamma production, unexpectedly enhanced later allergen-specific asthma and promoted dual allergen-specific T(H)1 and T(H)2 responses. Pulmonary dendritic cells obtained from the lung after viral clearance and resolution of acute inflammation conferred enhanced allergic disease and concurrent T(H)1 and T(H)2 immune responses, and these effects were dependent on IFN-gamma secreted during the acute viral infection. Thus, respiratory viral infection and the acute T(H)1 response can positively regulate T(H)2-dependent allergic pulmonary disease in vivo, at least in part, by altering pulmonary dendritic cell function.

Animals↗

PubMed2003

Detecting susceptibility genes in case-control studies using set association.

Complex diseases are generally caused by intricate interactions of multiple genes and environmental factors. Most available linkage and association methods are developed to identify individual susceptibility genes assuming a simple disease model blind to any possible gene - gene and gene - environmental interactions. We used a set association method that uses single-nucleotide polymorphism markers to locate genetic variation responsible for complex diseases in which multiple genes are involved. Here we extended the set association method from bi-allelic to multiallelic markers. In addition, we studied the type I error rates and power for both approaches using simulations based on the coalescent process. Both bi-allelic set association (BSA) and multiallelic set association (MSA) tests have the correct type I error rates. In addition, BSA and MSA can have more power than individual marker analysis when multiple genes are involved in a complex disease. We applied the MSA approach to the simulated data sets from Genetic Analysis Workshop 13. High cholesterol level was used as the definitive phenotype for a disease. MSA failed to detect markers with significant linkage disequilibrium with genes responsible for cholesterol level. This is due to the wide spacing between the markers and the lack of association between the marker loci and the simulated phenotype.

Adult Children↗

PubMedDate not supplied

BRCA status, molecular markers, and clinical variables in early, conservatively managed breast cancer.

Conservatively treated premenopausal breast cancer has a higher rate of local relapse as well as an increased genetic predisposition to cancer. The current study's purpose was to evaluate the interactions between BRCA-1/2 status and molecular biologic markers in a cohort of conservatively managed breast cancer patients. Seventy-six premenopausal women treated with breast-conserving surgery and radiation therapy were this study's focus. All patients were treated with wide local excision with or without axillary dissection, followed by radiation to the intact breast. Systemic therapy was administered as clinically indicated. All patients in this study had an available paraffin block from the primary tumor and agreed to undergo complete sequencing of the BRCA-1 and BRCA-2 genes. The primary breast tumor tissue from each patient was immunohistochemically stained for estrogen receptor (ER), progesterone receptor (PR), p53, HER-2/neu, and Proliferating Cell Nuclear Antigen (PCNA). Of the 76 patients tested for BRCA, 50 patients had wild-type BRCA-1 and BRCA-2, 15 had variants of unclear significance, 6 had deleterious mutations in BRCA-1, and 5 had deleterious mutations in BRCA-2. p53 positivity correlated with deleterious mutations in BRCA-1 (p = 0.023), but not in BRCA-2. Though not significant, there was a trend for ER and PR negativity to correlate with BRCA-1 mutation (p = 0.087 and 0.054, respectively); there were no correlations between ER, PR, and BRCA-2. Though not significant, all 11 tumors with BRCA mutations were HER-2/neu negative. Patients with BRCA mutations have a unique molecular profile. These data can be helpful in understanding differences in the biologic behavior of patients with familial breast cancers.

Adult↗

PubMedDate not supplied

Immunohistochemical biomarkers in patients with early-onset breast carcinoma by tissue microarray.

UNLABELLED: Young women with breast cancer have a poor prognosis, and the role of biologic markers in young women is not well defined. We investigated the association of estrogen receptor, progesterone receptor, Bcl-2, HER-2/neu, p53, and Ki-67 with clinicopathologic features and outcome in young women with breast cancer. METHODS: A cohort of 103 patients with early-onset breast cancer treated with conservative surgery and radiotherapy were entered in this study. Age range was 25-45 years, and median follow-up was 8.7 years. Each of the paraffin-embedded specimens was immunologically stained for six biomarkers expression by a recently developed tissue microarray method. RESULTS: The 10-year overall breast relapse-free and distant relapse-free survival rates were 82.7%, 84.6.4%, and 66.7%, respectively, with 14 local relapses and 26 distant metastases among the 103 patients evaluated. Positive expression of estrogen receptor, progesterone receptor, bcl-2, HER-2/neu, p53, and Ki-67 were 42.7%, 48.5%, 35.6%, 28.0%, 36.9%, and 39.7%, respectively. Tumor stage and nodal status were significantly associated with overall survival and distant metastasis-free rate in univariate and multivariate analysis. Progesterone receptor negativity and Ki-67 positivity were associated with distant metastasis. There was no statistically significant correlation between the six biomarkers and local relapse. CONCLUSIONS: Progesterone receptor, Ki-67, tumor stage, and nodal status were prognostic factors for distant failure in early-stage breast cancer in young patients. Further studies are needed to find other biologic markers associated with local failure in this group of patients.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

Preoperative plasma fibrinogen levels in gastric cancer patients correlate with extent of tumor.

BACKGROUND/AIMS: The aim of the present study was to investigate the relationship between the preoperative plasma fibrinogen level and the extent of tumor involvement in gastric cancer patients. METHODOLOGY: Preoperative plasma fibrinogen levels of 354 patients who underwent gastric cancer surgery were quantified using an immunoassay. The relationships between the plasma fibrinogen level and other prognostic variables (tumor size, macroscopic and histological type, depth of tumor invasion, presence of lymph node involvement and distant metastasis) were then examined using univariate and multivariate linear regression analyses. RESULTS: The plasma fibrinogen level was significantly lower in patients with early gastric cancer than in those with advanced gastric cancer (312+/-6.7 vs. 361.9+/-97.0 mg/mL, p<0.001). A significant relationship existed between the preoperative fibrinogen levels and the presence of metastatic lymph nodes (320+/-78.6 vs. 352.6+/-94.1 mg/mL, p=0.001) and distant metastasis (338.2+/-89.5 vs. 396.9+/-128.3 mg/mL, p=0.013). Size of the tumors and depth of tumor invasion could predict elevated fibrinogen levels positively in both the univariate regression and multivariate linear regression analyses. CONCLUSIONS: These data suggest that the plasma fibrinogen level is a clinically important and useful marker of the extent of tumor progression in gastric cancer.

Adult↗

PubMedDate not supplied

Laparoscopic "Dome-down" cholecystectomy with the LCS-5 Harmonic scalpel.

OBJECTIVE: Misidentification of ductal anatomy and electrocautery injuries are complications associated with laparoscopic cholecystectomy (LC). Dome-down LC creates a 360-degree view of the gallbladder-cystic duct junction, reducing the risk for anatomy misidentification. In addition, ultrasonic instrumentation eliminates the risk for electrocautery injuries. This study assessed the feasibility and safety of dome-down LC combined with ultrasound technology. METHODS: Patients with noncancerous gallbladder disease were enrolled consecutively. Gallbladders were classified by clarity (Class I to IV) of anatomy and pathology (acute, chronic, or acalculous). The gallbladder was dissected from the gallbladder bed using a dome-down technique, and the cystic artery was coagulated and transected with the LCS-5 Harmonic scalpel (Ethicon Endo-Surgery Inc., Cincinnati, Ohio). The cystic duct was ligated with 2-polydioxanone Endoloops size 2-0 and sharply divided, leaving one Endoloop on the cystic duct stump. RESULTS: LC was successfully completed in 105 patients (mean age, 44 years; range, 18 to 91 years) in whom the anatomy was classified as Class I in 30 (29%) patients, Class II in 42 (38%), Class III in 25 (24%), and Class IV in 8 (8%). Gallbladder dissection time ranged from 8 to 42 minutes (mean, 18 min). The operating room time ranged from 32 to 128 minutes (mean, 55 min). Two gallbladder perforations occurred, but no complications were associated with the extrahepatic biliary tree, viscera, or major blood vessels. Elective conversion occurred in 8 (7.6%) patients due to poor visualization of anatomy because of inflammation and adhesions. Patient blood loss was minimal in all cases. No postoperative complications were observed after a 6-month follow-up. CONCLUSION: Dome-down laparoscopic cholecystectomy with the LCS-5 Harmonic scalpel decreases the potential for misidentification of ductal anatomy, has minimal complications, and eliminates electrocautery risks. Conversion is related to poor visualization of anatomy due to inflammation and adhesions.

Adolescent↗