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Lee SH (lee + sh)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Current treatment strategies for pulmonary arterial hypertension

JOURNAL OF INTERNAL MEDICINE, Issue 3 2005
S. H. LEE
Abstract., Lee SH, Rubin LJ (University of California, San Diego, La Jolla, CA, USA). Current treatment strategies for pulmonary arterial hypertension (Review). J Intern Med 2005; 258: 199,215. Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, exercise tolerance, functional class, haemodynamics, echocardiographic parameters and quality of life measures. Since the introduction of continuous intravenous prostacyclin, the treatment armamentarium of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Selective endothelin-A receptor antagonists have shown promise in clinical trials and are likely to be added to the list of options. As the number of medications available for PAH continues to increase, treatment decisions regarding first-line therapy, combination treatments, and add-on strategies are becoming more complex. This article reviews the current treatments strategies for PAH and provides guidelines for its management. [source]

Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability

APMIS, Issue 5 2010
SANG YONG SONG
Song SY, Kang MR, Yoo NJ, Lee SH. Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability. APMIS 2010; 118: 389,93. Coordinated protein phosphorylation and dephosphorylation are crucial in the regulation of cell signaling, and disruption of the coordination is known to play important roles in cancer development. Recent reports revealed that classical protein tyrosine phosphatase (PTP)-encoded genes are somatically mutated in human colorectal cancer. However, data on dual specificity phosphatase (DPTP) gene mutations in human cancers are lacking. By analyzing a public genomic database, we found that five DPTP genes, CDC14A, MTM1, MTMR3, SSH1, and SSH2, have mononucleotide repeats in their coding DNA sequences. To see whether these genes are mutated in cancers with microsatellite instability (MSI), we analyzed the mononucleotide repeats in 26 gastric cancers (GC) with MSI (MSI-H), 12 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 33 colorectal cancers (CRC) with MSI-H, 14 CRC with MSI-L, and 45 CRC with MSS by single-strand conformation polymorphism (SSCP). We found CDC14A and MTMR3 mutations in five and one cancer (s), respectively. These mutations were detected in MSI-H cancers, but not in MSI-L or MSS cancers. The GC and CRC with MSI-H harbored the mutations in 15% and 6%, respectively. The CDC14A and MTMR3 mutations detected in the GC and CRC were deletion or duplication mutations of one base in the nucleotide repeats that would result in premature stops of the amino acid syntheses. Our data show that frameshift mutations of DPTP genes in MSI-H cancers occur at moderate frequencies. The data suggested that alterations in the CDC14A and MTMR3 genes may play a role in the development of GC and CRC with MSI-H by deregulating phosphatase functions possibly together with mutations of classical PTP genes. [source]

Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers

APMIS, Issue 4 2010
NAM JIN YOO
Yoo NJ, Hur SY, Kim MS, Lee JY, Lee SH. Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers. APMIS 2010; 118: 271,6. Evidence exists that microRNA (miRNA), which regulates gene expression, is frequently deregulated in cancers. A mature miRNA directs a RNA-induced silencing complex (RISC) to its target messenger RNA, and causes inhibition of gene transcription. Ago proteins and TNRC proteins are main components of the RISC and participate in miRNA-induced gene silencing. However, expression status of Ago and TNRC proteins has not yet been studied in human cancer tissues. In this study, we attempted to explore whether expressions of Ago2 and TNRC6A are altered in prostate carcinomas (PCA) and esophageal squamous cell carcinomas (ESCC). We analyzed the expression of Ago2 and TNRC6A in 107 PCA and 58 ESCC tissues by immunohistochemistry using a tissue microarray (TMA) method. In the prostate, Ago2 was not expressed in normal glandular cells, while it was expressed in 50.0% of prostate intraepithelial neoplasia (PIN) and 57.0% of the PCA. TNRC6A was not expressed in normal prostate cells, while it was expressed in 55.0% of the PIN and 63.6% of the PCA in cytoplasm and nucleus. In the esophagus, neither Ago2 nor TNRC6A was expressed in normal squamous cells, while Ago2 and TNRC6A were expressed in 58.6% and 62.1% of the ESCC, respectively. However, neither the expression of Ago2 or TNRC6A was associated with pathologic characteristics of the cancers, including age, sex, Gleason score (PCA) and stage. The increased expressions of Ago2 and TNRC6A in both PCA and ESCC compared with their normal cells suggested that over-expression of these proteins may be related to miRNA functions and might play a role in tumorigenesis of PCA and ESCC. [source]

Mutational analysis of caspase genes in prostate carcinomas

APMIS, Issue 4 2010
MIN SUNG KIM
Kim MS, Park SW, Kim YR, Lee JY, Lim HW, Song SY, Yoo NJ, Lee SH. Mutational analysis of caspase genes in prostate carcinomas. APMIS 2010; 118: 308,12. Evasion of apoptosis is one of the hallmarks of cancer. Of the components of apoptosis machinery, caspases are the main executioners of apoptosis that initiate and propagate the apoptosis, and finally degrade target molecules. Caspase-encoding genes have been reported to harbor inactivating mutations in many human cancers. However, mutational status of caspase genes in prostate carcinomas has not been identified. The aim of this study was to explore whether caspase genes are somatically mutated in prostate carcinomas. For this, we analyzed entire coding regions of 11 human caspase-encoding genes (CASP1,10 and 14) in 45 prostate carcinoma tissues by a single-strand conformation polymorphism (SSCP) assay. In this study, however, we detected no somatic mutation of CASP genes in the prostate carcinomas by the SSCP. This is the first report on systematic evaluation of caspase-encoding gene mutations in human prostate carcinomas, and our data indicate that CASP genes may not be mutated in prostate carcinomas. The data suggest that apoptosis evasion in prostate carcinoma may be dependent on other mechanisms besides genetic alteration of caspase-encoding genes. [source]

Immunohistochemical analysis of NF-,B signaling proteins IKK,, p50/p105, p52/p100 and RelA in prostate cancers

APMIS, Issue 8 2009
SEONG IL SEO
Seo SI, Song SY, Kang MR, Kim MS, Oh JE, Kim YR, Lee JY, Yoo NJ, Lee SH. Immunohistochemical analysis of NF-,B signaling proteins IKK,, p50/p105, p52/p100 and RelA in prostate cancers. APMIS 2009; 117:623,8. Activation of nuclear factor-kappa B (NF-,B) signaling is considered an important mechanism in the development of prostate cancers. A recent study revealed that I,B kinase epsilon (IKK,), an activator of NF-,B, was overexpressed in breast cancers and acted as an oncogene. Expression of NF-,B members has been reported in prostate cancer tissues, but expression of IKK, has not yet been studied in prostate cancers. In this study, we attempted to explore as to whether expressions of IKK, and NF-,B members p50/105, p52/p100 and RelA are altered in prostate cancers. We analyzed the expression of IKK,, p50/105, p52/p100 and RelA in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray (TMA) method. In the TMA, IKK, is expressed in basal cells, but not in alveolar cells in normal prostate glands. IKK, is expressed in 60.0% of prostate intraepithelial neoplasm (PIN) and 70.1% of the prostate cancers in the cytoplasm. Nuclear immunostainings of NF-,B members p50/105, p52/p100 and RelA, which are considered activation of NF-,B signaling, were observed respectively in 28.0%, 18.7% and 37.4% of the cancers. Nuclear staining was detected neither in normal alveolar cells nor in PIN. However, none of the expression of p50/105 nor p52/p100 nor RelA nor IKK, was associated with pathologic characteristics, including size of the cancers, age, Gleason score and stage. The increased cytoplasmic expression of IKK, as well as the increased nuclear expressions of p50/105, p52/p100 and RelA in the prostate cancers compared to normal alveolar cells suggested that overexpression of these proteins may be related to activation of the NF-,B pathway and might play a role in tumorigenesis of prostate cancers. [source]