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K Yun

Publications and source records attributed to K Yun.

At least 55 records · Page 3Linked to original sources
PubMed1996

Insulin-like growth factor II expression in primary meningeal hemangiopericytoma and its metastasis to the liver accompanied by hypoglycemia.

In situ hybridization and immunohistochemistry were performed to detect insulin-like growth factor II (IGF2) in tissue sections obtained from a patient with hypoglycemia in association with primary meningeal hemangiopericytoma and metastatic foci in the liver. High levels of IGF2 mRNA and IGF2 peptide were detected in both primary and metastatic tumor cells, although the serum IGF2 level was within the normal range. Because the serum level of IGF binding protein-3 was low, whereas the serum insulin level and other endocrinological examinations were normal, we speculate that the mechanism of the hypoglycemia was associated with the tumor-produced IGF2.

Female↗
PubMed1996

Skeletal muscle determination and differentiation: story of a core regulatory network and its context.

Regulation of skeletal muscle determination and differentiation in vertebrates centers on a core regulatory network which is composed of two families of transcription factors, the MyoD group basic helix-loop-helix (bHLH) muscle regulatory factors (MRFs) and the myocyte enhancer factor 2 (MEF2) group of MADS-box regulators. Members of this network interact with each other genetically and physically, and together they cooperate to positively regulate transcription of downstream muscle-specific differentiation genes. During development, the myogenic network can be activated or repressed in response to patterning signals, some of which have recently been identified. Once activated, the powerful myogenic activity of the core network can be modulated and held in check by a remarkably large group of negative regulators that operate on network components by diverse mechanisms. Recent discoveries highlight extensive parallels between myogenesis and peripheral neurogenesis in the structures of their respective regulatory networks and in the interaction of their bHLH networks with other regulatory circuits. Comparisons with Drosophila indicate that these ensembles of interacting molecular circuits have been highly conserved during evolution.

Animals↗
PubMed1996

Monoallelic expression of the insulin-like growth factor-2 gene in ovarian cancer.

Genomic imprinting is defined as a gamete-specific modification causing differential expression of the two alleles of a gene in somatic cells and is becoming increasingly recognized as playing an important role in a number of human diseases including cancer. We have reported that the loss of the insulin-like growth factor-2 (IGF2) gene imprinting results in the deregulation of both IGF2 alleles, which may contribute to the onset of Wilms tumor. It is important to see whether such abnormal genomic imprinting is implicated in the etiology of common adulthood cancers. In the present study we have examined the expression level and imprinting status of the IGF2 gene in human ovaries and ovarian cancers. We confirm that IGF2 is significantly expressed in ovaries and ovarian cancers. In normal ovaries, both surface epithelium and the ovary proper demonstrate monoallelic IGF2 expression. Among 27 tumors, all 11 heterozygous for the IGF2 locus show monoallelic IGF2 expression (2 of them are proven to be from the paternal allele). The data suggest that the increased IGF2 gene expression in ovarian cancer may be achieved by a mechanism other than loss of imprinting.

Alleles↗
PubMed1996

Increased expression of insulin-like growth factor 2 in hepatocellular carcinoma is primarily regulated at the transcriptional level.

To investigate the control mechanisms of insulin-like growth factor 2 (IGF2) gene expression, we studied 25 hepatocellular carcinomas (HCC) to compare the levels of total IGF2 mRNA and the IGF2 peptide by using in situ hybridization and immunohistochemistry, respectively. Increased expression of IGF2 mRNA and the IGF2 peptide was observed in 13 HCC. The spatial distribution and intensity of IGF2 mRNA in these 13 HCC was almost identical to that of the IGF2 peptide, which suggests that high IGF2 expression was primarily regulated at the transcriptional level. The levels of IGF2 gene expression in the 13 HCC seemed to be inversely correlated with the degree of tumor cell differentiation. Furthermore, in situ hybridization using probes specific to transcripts expressed from the IGF2 promoters P1 and P3 revealed that transcription was predominantly from P3 rather than from P1.

Adult↗
PubMed1996

Detection of micrometastases in colorectal cancer patients by K19 and K20 reverse-transcription polymerase chain reaction.

Tumor stage in bowel and breast cancer is the chief determinant of prognosis and the need for adjuvant therapy. The intermediate filament protein keratin 19 (K19) is expressed by epithelia and corresponding malignancies. Recently, the detection of K19 gene expression by RT-PCR has been reported as a sensitive tool for detecting occult metastasis to the lymph nodes and bone marrow of patients with primary epithelial tumors. Doubt has arisen, however, about the tissue specificity of K19 gene expression. In this study, we report a comparison of RT-PCR for K19 with another keratin, K20, in the lymph nodes and bone marrow of 15 patients with colorectal cancer, eight control patients who underwent bowel resection for benign disease, and four other control patients. K19 and K20 gene expression was detected in 84 and 26 of 109 lymph nodes and in 6 and 0 of 15 bone marrow aspirates, respectively, from colorectal cancer patients. K19 gene expression was also detected in 34 of 40 lymph nodes and in 5 of 12 bone marrow aspirates from control patients, whereas K20 gene expression was undetectable in any control sample. In conclusion, K19 RT-PCR lacks specificity as a marker of occult lymph node and bone marrow metastasis. In contrast, K20 RT-PCR was specific and should be evaluated further in future studies.

Colorectal Neoplasms↗
PubMed1995

Exclusion of the Wilms tumour gene (WT1) promoter as a site of frequent mutation in Wilms tumour.

WT1 is a tumour suppressor gene expressed in a specific temporal and spatial pattern in the developing kidney. Up to 15% of Wilms tumours have point mutations in the WT1 gene coding sequence. We have now investigated whether mutations in the WT1 promoter could be associated with loss of control WT1 expression and subsequent Wilms tumour formation. Using single-strand conformational polymorphism (SSCP) analysis we analysed 39 sporadic Wilms tumours for WT1 promoter mutations. We found six linked common sequence polymorphisms and two unlinked less frequent polymorphisms which allowed us to identify four tumours with loss of heterozygosity but none with point mutations, small deletions, insertions or rearrangements. We therefore conclude that WT1 promoter mutations are unlikely to play an important role in Wilms tumorigenesis.

Base Sequence↗
PubMed1995

Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma.

The expression of insulin-like growth factor 2 (IGF2) and insulin-like growth factor binding protein 2 (IGFBP2) in 11 cases of hepatoblastoma was studied by means of in situ mRNA hybridization using digoxigenin (DIG)-labeled riboprobes. The results showed that both IGF2 and IGFBP2 transcripts are present in hepatoblastoma and that their expression is inversely correlated with the degree of tumor cell differentiation. The data suggested that IGF2 and IGFBP2 gene expression could be regarded as a marker for assessment of the degree of differentiation in hepatoblastoma.

Carrier Proteins↗
PubMed1995

Establishment of functional imprinting of the H19 gene in human developing placentae.

We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.

Alleles↗
PubMed1995

Insulin-like growth factor II gene expression by congenital mesoblastic nephroma.

We studied the expression of insulin-like growth factor II (IGF2) and Wilms' tumor gene (WT1) in nine cases of congenital mesoblastic nephroma (CMN) and five cases of first trimester fetal kidneys by in situ hybridization. Our aim was to determine their site of expression and to correlate their histogenetic relationship to those of other childhood renal tumors. Our results showed that all nine cases of CMN (classic, mixed, and cellular) contained abundant IGF2 but not WT1 transcripts. The IGF2 transcripts were diffusely distributed over the tumor cells. These findings suggest that CMN is derived from primitive mesenchymal nephrogenic cells and have a potential to differentiate into a stromal cell lineage.

Female↗
PubMed1995

Comparative in situ hybridization analysis of PAX2, PAX8, and WT1 gene transcription in human fetal kidney and Wilms' tumors.

Wilms' tumor (WT) is a childhood renal neoplasm with histological features resembling fetal kidney development. Two members of the paired box family of genes, PAX2 and PAX8, are expressed in WT and are potentially involved in its induction. A zinc finger gene, WT1, which is involved in WT induction, encodes a DNA binding protein, and like PAX2 and PAX8 proteins is a transcription factor with an important role in kidney development. We have compared the expression patterns of PAX2, PAX8, and WT1 in fetal kidney and WTs by in situ hybridization. The PAX2, PAX8, and WT1 genes were transcribed in the condensed mesenchyme and early stages of epithelial differentiation in fetal kidney. WT1 gene transcription was observed in the glomeruli of fetal kidney until a later stage in development than PAX genes. In WTs all three genes were expressed in the condensed blastema, but WT1 expression was not detectable in the epithelial structures in two WTs. No evidence of attenuation of PAX gene expression was found in WT. These results suggest that in some WTs the expression of WT1 is attenuated in structures that continued to express PAX genes. It is unlikely that both PAX2 and PAX8 genes would be mutated in WT. However, failure of PAX gene expression to attenuate in WTs may result from mutations involved in the onset of the tumor.

DNA-Binding Proteins↗
PubMed1994

Molecular analysis of a patient with Beckwith-Wiedemann syndrome, rhabdomyosarcoma and renal cell carcinoma.

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.

Abdominal Neoplasms↗
PubMed1994

Mosaic and polymorphic imprinting of the WT1 gene in humans.

We have examined the imprinting of the Wilms' tumour suppressor gene (WT1) in human tissues. We confirm that WT1 is biallelically expressed in the kidney, however, in five of nine preterm placentae WT1 was expressed largely or exclusively from the maternal allele. Monoallelic expression of WT1 was also found in two fetal brains. These data demonstrate that WT1 can undergo tissue specific imprinting. Furthermore, because monoallelic expression of WT1 was not found in all placentae examined, WT1 imprinting may be genetically polymorphic within the human population.

Alleles↗
PubMed1994

Malignant rhabdoid tumor of the kidney expresses insulin-like growth factor II transcripts.

Insulin-like growth factor II (IGF-II) is thought to play a major role in fetal growth and development. High levels have been demonstrated in blastemal cells of both normal fetal kidney and Wilms' Tumor (WT). In this report, 2 cases of malignant rhabdoid tumor of the kidney (MRTK) were studied to detect the expression of IGF-II mRNA by in situ hybridization using 35S labelled RNA riboprobes. Results showed highly strong and specific IGF-II mRNA expression by tumor cells.

Child↗
PubMed1994

Evaluation of myocardial motion tracking with cine-phase contrast magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The accuracy of myocardial motion measurements, computed from cine-phase contrast (cine-PC) magnetic resonance (MR) velocity data, was compared with directly visualized motion of MR signal voids caused by implanted tantalum markers in anesthetized dogs. METHODS: Magnetic resonance imaging (MRI) data were electrocardiogram-gated and divided into 16 phases per cardiac cycle. Myocardial trajectories as a function of time in the cardiac cycle were measured using both methods for four to seven markers in each of eight animals. RESULTS: The peak observed in-plane excursion was 4.0 +/- 2.1 mm. The average deviation between displacements derived from velocity data versus displacements visualized directly was 1.1 +/- 0.7 mm (27.5% of the peak displacement). The difference was less if three separate MR scans were used to measure each velocity component in the cine-PC method. This improvement is probably caused by improved temporal resolution. CONCLUSIONS: Cine-PC MRI offers a noninvasive method for accurate quantification of myocardial motion.

Animals↗
PubMed1994

Expression of WT1 protein in fetal kidneys and Wilms tumors.

BACKGROUND: Wilms' tumors are embryonic kidney neoplasms believed to result from a perturbation in the development of the metanephric blastema. A candidate gene (WT1) has been cloned that has been found to be mutated in a number of Wilms' tumors, consistent with its suggested role as a tumor suppressor gene. This gene has been shown to be essential to the normal development of the embryonic kidney. EXPERIMENTAL DESIGN: The aim of the present study was to provide information on the level at which the WT1 gene is regulated. Immunohistochemistry, immunofluorescence, and in situ hybridization was used to examine the localization of WT1 protein and mRNA, respectively. We further used immunofluorescence to examine the WT1 expression in seven Wilms' tumors. RESULTS: In fetal kidneys, WT1 transcripts were detected with increasing levels of hybridization signal in induced blastemal cells, renal vesicles, pre-podocytes of comma- and S-shaped bodies, and podocytes of glomeruli. WT1 protein, detected by an antibody raised against recombinant WT1 fusion protein, was seen in the nuclei of the same cell types mentioned above, and the staining intensity was comparable to the levels of WT1 transcripts. Immunostaining of seven Wilms tumors demonstrated that WT1 protein was expressed only in neoplastic structures whose normal counterparts also expressed WT1 protein. Neither stromal cells nor rhabdomyoblasts contained WT1 protein. CONCLUSIONS: The results show that in fetal kidney, WT1 transcripts and protein are coordinately expressed, and strongly associated with differentiation of metanephric blastemal cells into epithelial cells. Furthermore, the finding that WT1 transcripts and protein are coordinately expressed, suggests that WT1 gene expression is primarily regulated at the level of transcription.

Blotting, Western↗
PubMed1993

Insulin-like growth factor II and WT1 transcript localization in human fetal kidney and Wilms' tumor.

In situ hybridization was used to examine, in parallel, the localization of insulin-like growth factor II (Igf2) and WT1 transcripts in normal fetal kidney and Wilms' tumor. The expression of Igf2 and WT1 transcripts in the fetal kidney is almost complementary in both the epithelial and stromal cell lineages derived from the undifferentiated metanephrogenic blastema. The patterns of transcription of Igf2 in three Wilms' tumors appeared to be perturbed as compared to the normal fetal kidney. In these tumors Igf2 transcripts were detected in structures that are developmentally equivalent to the renal vesicle, which in the normal kidney do not contain Igf2 transcripts. These results suggest that Wilms' tumors arise from an alteration in the regulation of Igf2 mRNA synthesis.

Base Sequence↗
PubMed1993

Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour.

Genomic imprinting has been implicated in the onset of several embryonal tumours but the mechanism is not well understood. Maternal chromosome 11p15 loss of heterozygosity and paternal chromosome 11 isodisomy suggest that imprinted genes are involved in the onset of Wilms' tumour and the Beckwith-Wiedemann syndrome. The insulin-like growth factor II (IGF2) gene located at 11p15.5 has been put forward as a candidate gene as it is maternally imprinted (paternally expressed) in the mouse, and is expressed at high levels in Wilms' tumours. We report here that the IGF2 gene is expressed from the paternal allele in human fetal tissue, but that in Wilms' tumour expression can occur biallelically. These results provide, to our knowledge, the first evidence that relaxation of imprinting may play a role in the onset of disease and suggest a new genetic mechanism involved in the development of cancer.

Alleles↗