Search PubMed⌕ Search

Biomedical subjects

K Yun

Publications and source records attributed to K Yun.

At least 19 recordsLinked to original sources
PubMed2001

Diagnostic use of the sentinel node in colon cancer.

PURPOSE: The aim of this study was to compare the lymphatic drainage of colon cancer with the anatomic distribution of histologic and submicroscopic lymph node metastases. METHODS: Patients attending for colectomy were eligible to enter the study. At the commencement of surgery, 40 MBq of 99mTc colloidal antimony sulfide in 2 ml of Patent Blue dye was injected subserosally around the tumor. Resection was completed in a standard fashion. After resection, specimens were imaged with a gamma camera to determine the site of sentinel lymph nodes, and then dissected, recording the position of the lymph nodes on an anatomic diagram. Recovered lymph nodes were bisected, one-half for routine histology and one-half for assessment by keratin 20 (K20) reverse transcription polymerase chain reaction. The kappa measure of agreement was used to assess concordance between sentinel nodes and histologic and submicroscopic metastases. RESULTS: Four hundred fifty-six lymph nodes were dissected from 26 tumors and evaluated using lymphoscintigraphy and lymph node mapping. Sentinel nodes were evident in 23 tumors (88 percent). The sensitivity of sentinel nodes involvement as a predictor of metastatic disease was 55 percent (95 percent confidence interval, 23-83), with a false negative (nondiagnostic) rate of 45 percent. Sentinel nodes involved the apical group in four tumors, and represented anatomic "skip" lesions in four tumors. CONCLUSIONS: Direct lymphatic drainage to the apical group does occur in colon cancer; however, sentinel node mapping of colon cancer by this technique is of little clinical value because of the poor concordance between lymph node metastases and sentinel nodes.

Adult↗
PubMed2001

Skip metastases in colon cancer: assessment by lymph node mapping using molecular detection.

BACKGROUND: Colon cancer has been assumed to spread sequentially through the regional lymphatic bed, with skip metastases occurring in only 1% to 3% of cases. Molecular techniques allow the detection of occult metastases, but to date have not been applied to assess the pattern of regional lymphatic spread of colon cancer. METHODS: Fifty-five tumors from 54 patients with colonic adenocarcinoma were studied. Lymph node mapping was performed on fresh colonic specimens recording the position of each node on an anatomical diagram. Half of each lymph node was submitted for routine histology examination and half assayed for keratin 20 gene expression by reverse transcription-polymerase chain reaction. Logistic regression was used to analyze the distribution of histologic and occult metastases. RESULTS: A total of 1084 lymph nodes were dissected (median, 19 nodes; range, 4-52). Sixty-four lymph nodes from 20 tumors had histologically evident metastases and 76 lymph nodes from 13 tumors had occult metastases. There was no difference in the distribution of either histologic or occult metastases among paracolic, intermediate, and apical node groups. Ten patients had evidence of anatomical skip lesions after lymph node mapping and molecular analysis, only 1 of which was histologically detectable. CONCLUSIONS: This study demonstrates a higher incidence of skip metastases in colon cancer assessed by molecular techniques than has previously been reported, challenging the concept of sequential development of early lymph node metastases.

Actins↗
PubMed2001

Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon.

The telencephalon has two major subdivisions, the pallium and subpallium. The pallium, which primarily consists of glutamatergic cortical structures, expresses dorsal molecular markers, whereas the subpallium, which primarily consists of the GABAergic basal ganglia, expresses ventral molecular markers. Here, we present evidence that the progenitor and postmitotic cells flanking the pallial/subpallial boundary (PSB) in the embryonic mouse can be subdivided into multiple regions that express unique combinations of transcription factors. The domains that immediately flank the PSB are the ventral pallium (VP) and the dorsal lateral ganglionic eminence (dLGE). The early expression of the Pax6 and Gsh2 homeobox transcription factors overlaps in the region of the dLGE. Analyses of mice that lack functional alleles of either Gsh2 or Pax6 demonstrate that these genes have complementary roles in patterning the primordia flanking the PSB. In the Gsh2 mutants, the dLGE is respecified into a VP-like structure, whereas in the Pax6 mutants the VP is respecified into a dLGE-like structure. The role of Pax6 in dorsalizing the telencephalon is similar to its role in the spinal cord, supporting the hypothesis that some dorsoventral patterning mechanisms are used at all axial levels of the central nervous system.

Animals↗
PubMed2000

Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/- mutant mice.

PAX2 mutations cause renal-coloboma syndrome (RCS), a rare multi-system developmental abnormality involving optic nerve colobomas and renal abnormalities. End-stage renal failure is common in RCS, but the mechanism by which PAX2 mutations lead to renal failure is unknown. PAX2 is a member of a family of developmental genes containing a highly conserved 'paired box' DNA-binding domain, and encodes a transcription factor expressed primarily during fetal development in the central nervous system, eye, ear and urogenital tract. Presently, the role of PAX2 during kidney development is poorly understood. To gain insight into the cause of renal abnormalities in patients with PAX2 mutations, kidney anomalies were analyzed in patients with RCS, including a large Brazilian kindred in whom a new PAX2 mutation was identified. In a total of 29 patients, renal hypoplasia was the most common congenital renal abnormality. To determine the direct effects of PAX2 mutations on kidney development fetal kidneys of mice carrying a Pax2 (1Neu)mutation were examined. At E15, heterozygous mutant kidneys were approximately 60% of the size of wild-type littermates, and the number of nephrons was strikingly reduced. Heterozygous 1Neu mice showed increased apoptotic cell death during fetal kidney development, but the increased apoptosis was not associated with random stochastic inactivation of Pax2 expression in mutant kidneys; Pax2 was shown to be biallelically expressed during kidney development. These findings support the notion that heterozygous mutations of PAX2 are associated with increased apoptosis and reduced branching of the ureteric bud, due to reduced PAX2 dosage during a critical window in kidney development.

Adolescent↗
PubMed2000

Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations.

Lymph node status has major prognostic importance in colorectal cancer and greater precision in the diagnosis of lymph node metastases should provide better prognostic and therapeutic guidance. Keratin 20 (K20) gene expression has been used as a marker of lymph node metastases, but the evidence for this remains circumstantial. This study has therefore sought to determine K20 specificity and to correlate K20 expression with mutant K-RAS expression, in order to provide direct evidence that K20 expression in lymph nodes of colorectal cancer patients genuinely reflects metastatic disease. Specificity of K20 expression was established against a range of tissue types and 289 lymph nodes from 41 non-cancer control patients. K20 expression was restricted to gastrointestinal epithelia and was only present in one of the 289 control lymph nodes, giving a calculated specificity of 97.6% (95% confidence limits: 87.1-99.9%). Forty-two tumour samples were analysed for the presence of K-RAS codon 12 gene mutations using a RT-PCR mutant allele-specific amplification (MASA) technique. Thirteen tumours (31%) had codon 12 mutations detected by MASA and these were further analysed to determine the exact nature of the mutation. MASA was then used to screen the lymph nodes from these patients for the presence of the tumour-specific K-RAS transcript and the results were compared with K20 RT-PCR and histopathology from the same samples. Whilst K-RAS MASA was not as sensitive as K20 RT-PCR, there was substantial agreement between the assays. There were no K20-negative lymph nodes which were found to be K-RAS MASA-positive, whereas seven nodes in four patients were K20-positive and K-RAS-negative, in keeping with the differences in assay sensitivity. These results further validate K20 as a marker by providing greater certainty that what is being detected represents occult metastatic disease.

Biomarkers, Tumor↗
PubMed2000

Authors' reply

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Analysis of IGF2 gene imprinting in breast and colorectal cancer by allele specific-PCR.

The insulin-like growth factor II (IGF2) gene is imprinted with the paternal allele expressed and the maternal one silent. Loss of imprinting (LOI) of IGF2 has been suggested to play a role in the development of tumours, but the reported incidence of IGF2 LOI in tumours shows considerable variation, which may stem from different methodologies employed. In particular, partial digestion of reverse transcriptase-polymerase chain reaction (RT-PCR) products by restriction enzymes can lead to inaccurate measurements. To overcome the problem of partial enzymatic digestion, a novel method termed allele specific-polymerase chain reaction (AS-PCR) has recently been reported, which provides a significant advance over enzymatic digestion. A second problem with measurements of biallelic IGF2 transcription is that the co-amplification of contaminating genomic DNA during the RT-PCR step can lead to an overestimation of the frequency of biallelic IGF2 expression. To investigate the extent of this problem, total RNA from breast and colorectal cancer was analysed using two methods. The first method involved a first-round PCR using cDNA generated with primers spanning exons 8 and 9 (exon connection), followed by a second round of AS-PCR using primers from within exon 9. The second method used only AS-PCR with primers from within exon 9. The result was that the exon-connection approach was more accurate, thereby highlighting a significant problem in imprinting analyses where genomic DNA contamination cannot be completely ruled out.

Alleles↗
PubMed1999

Repeat-directed isolation of a novel gene preferentially expressed from the maternal allele in human placenta.

Using a repetitive sequence of tandemly arrayed pentanucleotides in the human H19 3'-flanking region, we isolated a phage clone (lambda PEN11) which localized to chromosome 11p15.5. The lambda PEN11 phage encodes a 2.3-kb cDNA consisting of seven exons at least. The gene was mainly expressed in brain and pancreas (and less abundantly in testis), and demonstrated differential allele usage, with maternal expression being predominant in placenta, which indicates the gene is an atypical imprinted gene. While the pentamer repeat might contribute to this effect, it is also possible that the differential allele usage might reflect the local chromosomal structure known as the imprinting domain.

Alleles↗
PubMed1999

Rapid identification of an A1555G mutation in human mitochondrial DNA implicated in aminoglycoside-induced ototoxicity.

This article describes a multiplex allele-specific PCR (AS-PCR) approach for detection of an A to G mutation occurring in the human mitochondrial 12s RNA gene at nucleotide 1555. Possession of this mutation has been shown to be associated with irreversible hearing loss following administration of aminoglycoside antibiotics, and in some families is associated with profound sensorineural deafness in the absence of aminoglycoside antibiotics. We screened 206 unrelated individuals from the province of Otago, New Zealand, and found one who possessed the mitochondrial 1555 A to G mutation (0.48%; 95% confidence interval, 0.01-2.75).

Aminoglycosides↗
PubMed1999

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer.

We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions.

Biomarkers, Tumor↗
PubMed1999

Large cell neuroendocrine carcinoma of the uterine cervix: a report of a case with coexisting cervical intraepithelial neoplasia and human papillomavirus 16.

Large cell neuroendocrine carcinomas (LCNECs), one of the four newly categorised endocrine tumors of the uterine cervix, are unusual and aggressive tumors. The present report describes a case of LCNEC diagnosed at an early stage and associated with cervical intraepithelial neoplasia (CIN). The LCNEC showed organoid and trabecular growth patterns and was positive for chromogranin and synaptophysin. The CIN lesion was of a high grade and was negative for these neuroendocrine markers. Polymerase chain reaction (PCR) using genomic DNA extracted from archival tissue demonstrated human papillomavirus (HPV) type 16 DNA in both the LCNEC and CIN lesions. These histological, immunohistochemical and PCR findings suggested that the LCNEC lesion was distinct from the CIN lesion and that both resulted from the carcinogenic field effect of HPV 16.

Adult↗
PubMed1999

Methylation imprinting of H19 and SNRPN genes in human benign ovarian teratomas.

In humans, studies of female germ cells are very limited by ethics. The current study investigated the usefulness of benign ovarian teratomas as a substitute for ova in analyses of imprinted genes. Twenty-five human benign ovarian teratomas were typed with 45 microsatellite DNA markers and classified according to their genotypic features. Two oppositely imprinted genes, H19 and SNRPN, were then chosen for analysis of their methylation states in these tumors. These analyses revealed that benign ovarian teratomas consist of a mixture of genetically and epigenetically heterogeneous cell populations. In contrast to previous reports, we could document only one case rising from germ cells by meiosis-II nondisjunction. H19 and SNRPN were methylated in individual teratomas to various degrees, ranging from normal somatic cell to expected ovum levels. The allele with residual methylation of H19 was consistent with that methylated in the patient's blood DNA, thus being of paternal origin. Degrees of H19 hypomethylation and SNRPN hypermethylation increased as the cellular origin of the tumors advanced in oogenesis and were closely correlated in individual teratomas. These results could be best explained by the assumption that the primary imprinting is a progressively organized process and suggest that the establishment of primary imprints on different genes might be mechanistically linked, even when those genes are oppositely imprinted.

Autoantigens↗
PubMed1999

Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis.

Herein we review the evidence that neocortical projection neurons and interneurons are derived from distinct regions within the telencephalon. While neocortical projection neurons are derived from the ventricular zone of the neocortex, neocortical interneurons appear to be derived from the germinal zone of the basal ganglia. These interneurons follow a tangential migratory pathway from the ganglionic eminences to the cortex. Interneurons of the olfactory bulb follow a distinct tangential migration from the basal ganglia. The Dlx homeobox genes, which are essential for basal ganglia differentiation, are also required for the development of neocortical and olfactory bulb interneurons. Furthermore, evidence is presented that retroviral-mediated expression of DLX2 in neocortical cells can induce GABAergic interneuron differentiation.

Animals↗
PubMed1999

Interactions between light and melatonin on the circadian clock of mice.

Melatonin and light synchronize the biological clock and are used to treat sleep/wake disturbances in humans. However, the two treatments affect circadian rhythms differently when they are combined than when they are administered individually. To elucidate the nature of the interaction between melatonin and light, the present study assessed the effect of melatonin on circadian timing and immediate-early gene expression in the suprachiasmatic nucleus (SCN) when administered in the presence of light. Male C3H/HeN mice, housed in constant dark in cages equipped with running wheels, were treated with either melatonin (90 microg, s.c.) or vehicle (3% ethanol-saline) 5 min prior to exposure to light (15 min, 300 lux) at various times in the circadian cycle. Combined treatment resulted in lower magnitude phase delays of circadian activity rhythms than those obtained with light alone during the early subjective night and advances in phase when melatonin and light were administered during the subjective day (p < .001). The reduction in phase delays with combined treatment at Circadian Time (CT) 14 was significant when light exposure measured 300 lux but not at lower light levels (p < .05). When light preceded melatonin administration, the inhibition of phase delays attained significance only when the light exposure reached 1000 lux (p < .05). Neither basal nor light-induced expression of c-fos mRNA in the SCN was modified by melatonin administration at CT 14 or CT 22. Together, these results suggest that combined administration of melatonin and light affect circadian timing in a manner not predicted by summing the two treatments given individually. Furthermore, the interaction is not likely to be due to inhibition of photic input to the clock by melatonin but might arise from a photically induced enhancement of melatonin's actions on circadian timing.

Animals↗
PubMed1999

Detection and significance of minimal residual disease in colorectal cancer.

Colorectal cancer (CRC) is one of the most common causes of cancer death in the developed world. Although the primary treatment for CRC is surgical, disease relapse due to minimal residual disease (MRD) following apparently curative surgery occurs in up to fifty percent of patients. Most patients who develop overt metastases beyond the regional lymph nodes eventually die of the disease. At present adjuvant chemotherapy is used to improve survival in patients with metastases to regional lymph nodes demonstrated by routine histopathology with no other evidence of spread. The ability to identify metastatic disease at an earlier stage could be of considerable benefit in directing adjuvant therapy to patients at high risk of relapse who are not identified by current methods. Several techniques have been developed for the detection of MRD, including immunohistochemical and molecular methods, however their role in clinical practise is not yet established. The purpose of this paper is to review these techniques and their potential clinical use in the management of CRC.

Colorectal Neoplasms↗