Biomedical subjects

C W Wu

Publications and source records attributed to C W Wu.

At least 91 records · Page 5Linked to original sources

PubMed1998

Serum progesterone levels in patients with gastric adenocarcinoma before and after gastrectomy.

BACKGROUND: Having observed that progesterone receptors exist in all gastric carcinoma tissues, the authors determined that serum progesterone levels in gastric carcinoma patients were worthy of evaluation. METHODS: Serum progesterone levels were determined in patients with gastric adenocarcinoma and in patients with benign disease who served as controls. All female patients were older than 55 years. The clinicopathologic significance of their serum progesterone levels was determined. RESULTS: In male patients (n = 122), the serum progesterone level (mean +/- standard deviation) was significantly higher than in the male control group (n = 163) (0.264+/-0.261 vs. 0.142+/-0.113 ng/mL; P < 0.001) and showed a tendency to be stage-related (P = 0.029). Serum progesterone levels significantly decreased after gastrectomy in patients with disease at Stage I (n = 27), II (n = 20), and III (n = 32), but not IV (n = 7). In 11 patients who died of recurrence, the serum progesterone levels were decreased when they were disease free but raised when recurrence was clinically evident. Patients with serum progesterone levels > 0.264 ng/mL survived for significantly shorter periods than those with levels < or = 0.264 ng/mL (P = 0.039). However, serum progesterone level was not an independent predictor of survival. Among the female patients (n = 12), the serum progesterone level (mean +/- standard deviation) of patients with gastric carcinoma was 0.427+/-0.428 ng/mL, whereas that of the control group (n = 17) was 0.217+/-0.451 ng/mL; the difference was statistically significant (P = 0.02). In female disease free patients studied postoperatively, the progesterone after gastrectomy showed a tendency to decrease, but this difference was not statistically significant (0.444+/-0.368 vs. 0.175+/-0.150 ng/mL; P = 0.091; n = 7). CONCLUSIONS: These data suggest that serum progesterone level reflects the presence or absence of gastric carcinoma by some unknown mechanism.

Adenocarcinoma↗

PubMed1998

Diagnostic and prognostic values of plasma levels of fibrinolytic markers in gastric cancer.

In the present study, we determined the plasma and tissue concentrations of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2 and urokinase-type plasminogen activator receptor in 32 patients with pathology-proved gastric cancer. The plasma levels of the same markers were compared in 37 patients with benign gastric ulcer in order to find out if these plasma levels could be used to evaluate the prognostic value in patients with gastric cancer. Plasma plasminogen activator inhibitor-1 was significantly higher in gastric cancer than in benign gastric disease (p < 0.0005), whereas plasma urokinase-type plasminogen activator was significantly lower in patients with gastric cancer than in those with benign ulcer (p = 0.003). There was no significant correlation between tissue and plasma concentrations of the same parameters. The plasma and tissue levels of fibrinolytic parameters were not affected by tumor size or distant metastasis, whereas tumor tissue concentration of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-2 were significantly higher in N0 than in N1 and N2, and tissue plasminogen activator inhibitor-1 was significantly higher in N0 than in N1. Plasma levels of the five fibrinolytic parameters could not take the place of the corresponding tissue concentrations on the diagnosis and prediction of prognosis in patients with gastric cancer. Tissue concentrations of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-2, especially the latter, can be used to predict lymph node involvement in patients with gastric cancer.

Aged↗

PubMed1998

Detection and quantitation of circulating cancer cells in the peripheral blood of lung cancer patients.

Detection and quantitation of circulating cancer cells in peripheral blood may improve cancer staging and monitoring. This study explored the feasibility of using circulating cancer cell detection in peripheral blood for the rapid assessment of chemotherapeutic response. Cytokeratin 19 mRNA was amplified by nested reverse transcriptase-PCR in the peripheral blood of 29 healthy volunteers, 33 pneumonia patients, and 86 lung cancer patients. Circulating cancer cells in the peripheral blood were semiquantitatively determined by taking the ratio of cytokeratin 19 band intensity from the second round of nested PCR to the glyceraldehyde-3-phosphate dehydrogenase band intensity from the first round of PCR amplification. The detection limit of the method was 1 cancer cell in 107 peripheral blood mononuclear cells. The positive detection rate was 40% for lung adenocarcinoma patients of all stages, 41% for squamous carcinoma patients of all stages, and 27% for small cell lung cancer patients. Only one control sample from a pneumonia patient showed a positive result (1.6%). The quantitative method reliably and sensitively estimated cancer cell numbers in the peripheral blood of lung cancer patients. Serial measurement of the relative number of circulating cancer cells correlated with the tumor burden and treatment response of patients. This method may help rapidly assess the efficacy of anticancer treatment, redefine cancer staging, and facilitate the design of better therapeutic strategies for the treatment of cancer patients.

Adult↗

PubMed1998

Morphology of M-cell axon arbors in striate cortex of monkeys reared with monocular aphakia.

Although the effects of visual deprivation on the development of ocular dominance columns have been well described in primates, nothing is known in primates about the impact of the deprivation on the axonal profiles that make up the ocular dominance columns. We now show that the effects of monocular deprivation on the morphology of geniculostriate axons involve not only shifts in terminal arbor sizes, much as would be expected from the ocular dominance data, but also changes in the proliferation of terminal arbor branches. In macaque monkeys reared from birth with unilateral lens removal (aphakia), terminal arbors of geniculostriate axons were bulk-filled with horseradish peroxidase (HRP) in brain-slice preparations and reconstructed from serial sections through striate cortex (area 17). Our focus was on the arbors that terminate in the upper tier of layer IV, the target of cells in the magnocellular (M) layers of the LGN. Of the 26 M-cell arbors reconstructed from three aphakic monkeys, eight were unique in having few very simple terminal arbor branches. These also tended to be smaller in total extent than the average M-cell axons reconstructed from 1 normal monkey. In contrast, eight arbors had very rich terminal branching patterns, and seven of these were larger than any of those from the normal monkey. We propose that the small, sparse axon arbors are related to the deprived eye, and the large, dense arbors are related to the non-deprived eye. These morphological changes reflect abnormalities in the growth patterns of geniculostriate inputs that undoubtedly have important persisting consequences for visual performance.

Animals↗

PubMed1998

Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family--implications for etiology of fetal alcohol syndrome and alcohol-related diseases.

The alcohol dehydrogenase (ADH) family is involved in the metabolism of both ethanol and retinoids. To quantitatively assess the potential contributions to first-pass metabolism of ethanol and the ethanol interference with retinoid homeostasis, saturation kinetics for ethanol oxidation as well as inhibition kinetics by ethanol for all-trans-retinol oxidation of human class I alpha alpha, beta1beta1, beta2beta2, gamma1gamma1, class II pi pi, class III chi chi, and class IV mu mu were evaluated and compared. Class I and class II ADHs exhibited substrate inhibition with inhibition constants ranging over 250-720 mM (except gamma1gamma1) ethanol. Class IV ADH displayed no appreciable inhibition up to 1 M ethanol. Activity of the class III enzyme (190 nM subunit) was undetectable at 250 mM ethanol. The kinetic simulations indicate that the hepatic pi pi and the gastric mu mu can most effectively contribute to first-pass metabolism of alcohol. The Michaelis constant (Km), turnover number (k(cat)), and catalytic efficiency (k(cat)/Km) for retinol oxidation relative to that for ethanol oxidation in class I, class II, and class IV ADHs ranged over 0.00022-1.3, 0.071-0.48, and 0.24-650, respectively. Ethanol was a competitive inhibitor against retinol for class I, II, and IV ADHs with apparent inhibition constants ranging over 0.037-11 mM, indicating that retinoic acid synthesis through the ADH pathways can be tremendously blocked during social/heavy drinking. These findings support the notion that first-pass metabolism of alcohol may occur mainly in the liver through class II pi pi and that cellular retinoid signaling may be perturbed by ethanol via ADH pathways.

Alcohol Dehydrogenase↗

PubMed1998

Lectin coprecipitative isolation from crudes by Little Rock Orange ligand.

Matrix ligands are intended for upstream use with dilute crudes on a large scale, splitting out sought-for proteins by coprecipitating them as dense, protected aggregates. Matrix ligand coprecipitation is rapidly, quantitatively reversible, by pH shifting and trapping matrix ligands on ion exchange resin, releasing the sought-for protein. Four lectins, wheat germ agglutinin, peanut lectin, concanavalin A, and Phaseolus vulgaris (red kidney bean) lectins, were coprecipitated from crude extracts, 0.05 to 0.4% crude protein, in a single step using Little Rock Orange matrix ligand. All were compared in specific activities (erythrocyte agglutination) and in SDS-PAGE analysis with the four corresponding commercial lectins purified by affinity chromatography. All four matrix-coprecipitated ligands were specifically active within range of the corresponding vendor (Sigma Co.) affinity chromatography-purified lectins. The matrix ligand coprecipitative technique requires optimization of ligand-protein (crude) ratios, denoted y, and determination of suitable pH ranges for coprecipitation relative to lectin isoelectric pH. These parameters control electrostatic ion pair association: ligand head anion binding to cationic target proteins. The coprecipitative and protective powers of new ligands like Little Rock Orange, their ability to scavenge sought-for lectins from dilute crudes, depend on ligand organic tail-tail association. After the strong anion heads of ligands bind to cationic proteins, their organic tails stack and draw the ligand-protein complexes together as aggregated coprecipitates.

Chemical Precipitation↗

PubMed1998

Correlation of hepatocyte growth factor-induced proliferation and calcium-activated potassium current in human gastric cancer cells.

Hepatocyte growth factor (HGF) has been found to stimulate proliferation and migration of human gastric carcinoma cells. Whether the HGF-induced responses are correlated with the expressed level of HGF receptors or the changes of ionic currents is not clear. The present study investigated the effects of HGF on the proliferation and ionic currents of two human gastric adenocarcinoma cell lines, which were found to express different amounts of HGF receptor. Results showed that HGF induced a dose-dependent growth stimulation and accelerated cell cycle progression in SC-M1 cells. In patch clamp study, HGF treatment induced an outward K+ current and increased the slope conductance at -80 mV from 110+/-15 pS/pF to 207+/-15 pS/pF. The HGF-induced K+ current was abolished when tetraethylammonium chloride was added in bathing solution or a low Ca2+ solution was included in the recording pipette. Furthermore, HGF (10 ng/ml) induced an oscillatory Ca2+-activated K+ current with a lag period of 5+/-3 min in SC-M1 cells. In contrast, HGF did not induce mitogenesis, cell cycle progression and changes in ionic currents in KATO-III cells, although this cell line expressed a higher level of HGF receptors than SC-M1 cells did. These findings provide evidence that the activity of Ca2+-activated K+ channel may be involved in the HGF-induced cell proliferation in human gastric cancer cells, but it did not correlate with the density of HGF receptors.

Adenocarcinoma↗

PubMed1998

Physical association between the EBV protein EBNA-1 and P32/TAP/hyaluronectin.

Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is a protein expressed constitutively during EBV latency. It is required to support the replication of the EBV genome once per cell cycle via the latent origin of replication, oriP. EBNA-1 also can activate transcription through binding to the family repeats of oriP. We wished to identify candidate cellular protein(s) that may interact with EBNA-1 and mediate these functions. A 32-kd protein was co-immunoprecipitated with EBNA-1 from 293 cells using a monoclonal antibody EBNA.OT1x. The regions of EBNA-1 which interact with this protein were studied using two deletion clones and mapped to EBNA-1 residues 1-102 and 325-357. Deletion of this region was shown previously in a mutant of EBNA-1 which had dominant-negative effects on both DNA replication and transactivation assays. The 32-kd protein was found to react with a polyclonal antiserum against P32/TAP (HIV Tat associated protein), which is known to interact with other RNA binding proteins and the RNA splicing factor SF2. The function of P32 was therefore proposed to involve RNA processing. In addition, this molecule was recently identified as hyaluronectin, which binds hyaluronic acid. Because several reports documented that intracellular hyaluronic acid can potentially affect cell proliferation, the association between EBNA-1 and P32/TAP/hyaluronectin may help the maintenance of episomal viral DNA within proliferating cells.

Animals↗

PubMed1998

Protein-tyrosine kinase and protein-serine/threonine kinase expression in human gastric cancer cell lines.

Protein kinases play key roles in cellular functions. They are involved in many cellular functions including; signal transduction, cell cycle regulation, cell division, and cell differentiation. Alterations of protein kinase by gene amplification, mutation or viral factors often induce tumor formation and tumor progression toward malignancy. The identification and cloning of kinase genes can provide a better understanding of the mechanisms of tumorigenesis as well as diagnostic tools for tumor staging. In this study, we have used degenerated polymerase-chain-reaction primers according to the consensus catalytic domain motifs to amplify protein kinase genes (protein-tyrosine kinase, PTK, and protein-serine/threonine kinase, PSK) from human stomach cancer cells. Following amplification, the protein kinase molecules expressed in the gastric cancer cells were cloned into plasmid vectors for cloning and sequencing. Sequence analysis of polymerase-chain-reaction products resulted in the identification of 25 protein kinases, including two novel ones. Expression of several relevant PTK/PSK genes in gastric cancer cells and tissues was further substantiated by RT-PCR using gene-specific primers. The identification of protein kinases expressed or activated in the gastric cancer cells provide the framework to understand the oncogenic process of stomach cancer.

Amino Acid Sequence↗

PubMed1998

Weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin: an effective chemotherapy in advanced gastric cancer.

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.

Adult↗

PubMed1998

Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter.

BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.

Adult↗

PubMed1998

Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma.

Ki-67 expression in tumours has been shown to be associated with prognosis in patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples were obtained from 67 patients undergoing surgical resection. None of these patients had been subjected previously to any other form of therapy, such as arterial embolization or chemotherapy. Histologically normal liver tissues from liver resection for metastatic colon cancer were taken as controls (n = 8). Monoclonal antibody against Ki-67 was used for immunostaining and flow cytometry was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage of Ki-67-positive cells) of the HCC (26 +/- 22%; range 0.1-89%) was significantly higher than that of the normal controls (39 +/- 0.8%, P < 0.05). The mean Ki-67 labelling index (19 +/- 15%; n = 28) of the tumours with diploid DNA pattern was significantly lower than those with aneuploid DNA pattern (32 +/- 25%, n = 39; P = 0.01). Hepatocellular carcinoma patients (n = 47) with Ki-67 index > 10% had a significantly lower disease-free and overall survival than those (n = 20) with Ki-67 index < or = 10% (P = 0.0009 and P = 0.02, respectively). Multivariate analysis showed that Ki-67 expression and tumour node metastasis stage were two independent prognostic factors for disease-free and overall survival rates. Our results suggest that the expression of Ki-67 is an independent prognostic indicator for patients with HCC after resection and could be of assistance in the decision-making of adjuvant therapy.

Aged↗

PubMed1998

Cordyceps sinensis increases the expression of major histocompatibility complex class II antigens on human hepatoma cell line HA22T/VGH cells.

Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression.

Carcinoma, Hepatocellular↗

PubMed1998

Genetic heterogeneity for familial hypertrophic cardiomyopathy in Chinese: analysis of six Chinese kindreds.

OBJECTIVE: Familial hypertrophic cardiomyopathy (FHCM) is a primary myocardial disease characterized by unexplained ventricular hypertrophy. The application of the techniques of reverse genetics has identified at least five chromosomal loci as the major causes for FHCM in diverse ethnic populations, suggesting substantial genetic heterogeneity for FHCM. Recently, the defective gene loci of two Chinese families with FHCM have been mapped to chromosome 11 and 14q1, respectively. For further understanding of the molecular basis of FHCM in Chinese, we analyzed the linkage between four other Chinese kindreds and DNA markers from chromosome 14q1. METHODS: Six unrelated Chinese families with FHCM, including two previously reported, were studied. Totally 90 family members were included for analysis. DNA from 80 individuals was extracted and polymerase chain reactions were performed using the primers designed according to the sequences derived from the alpha and beta myosin heavy chain gene. Totally four polymorphisms were studied, including three polymorphic microsatellite sequences and one single strand conformation polymorphism. Genetic linkage analysis were performed using the Linkage program. RESULTS: In the six studied families, 39 of the 90 family members were found to be affected diagnosed either by echocardiography or by clinical evaluation. The pattern of inheritance in all six studied families was most consistent with an autosomal dominant trait with a high degree of penetrance. Genetic linkage analysis using polymorphisms on the alpha and beta MHC genes showed a combined maximal lod score of 6.2 for trinucleotide repeat polymorphism AMHC-I 15 at theta = 0.00 for three studied families without recombination. Exclusion of linkage to the chromosome 14q1 location was noted in two of three other families with the maximal lod score of -2 or less. CONCLUSIONS: These results provide further evidence that FHCM in Chinese is genetically heterogeneous. Chromosome 14q1 locus, probably the beta myosin heavy chain gene, is important as the molecular basis for FHCM in Chinese.

Adolescent↗

PubMed1998

A modified design of microwave tissue coagulator monopolar antenna for applications in laparoscopic hepatic surgery.

Massive hemorrhage is of primary concern during hepatic surgery. In this study, we not only modified the monopolar antenna of the microwave tissue coagulator but also investigated its feasible applications in laparoscopic hepatic surgery. In addition, the conventional antenna of the microwave tissue coagulator was used as a model. A catheter was attached to the antenna. The network analyzer was used to analyze the impedance of the novel monopolar antenna. Moreover, we designed and constructed a novel monopolar antenna for the microwave tissue coagulator. The antenna is gas-leak-proof, having sufficient stiffness and length and retaining similar microwave emission strength, pattern, and shielding property as the conventional antenna. In vitro tests in porcine liver confirm the coagulation and hemostatic effects of the novel type laparoscopic monopolar antenna. Results presented herein confirm the effectiveness of a laparoscopic monopolar antenna for a microwave tissue coagulator with sufficient coagulation effects.

Animals↗

PubMed1997

Class I and class II major histocompatibility complex antigens expression on human hepatocytes and hepatoma cells: an approach with high sensitivity and specificity.

The expression of gene products of the major histocompatibility complex (MHC) on the cell surface is known to play an important role in immunological responses. While some studies have reported the presence of MHC antigens on hepatocytes, information about specific, sensitive hepatocyte MHC antigen expression in various liver diseases is minimal. To investigate the expression of class I and class II MHC antigens on hepatocellular carcinoma (HCC) specimens, two-color flow cytometry was used to demonstrate MHC antigen expression on non-malignant and malignant hepatocytes using the hepatocyte-specific monoclonal antibody (MAb) 9B2 for selective gating and either MHC-specific W6/32 (class I) or Q5/13 (class II) MAb for MHC antigen detection. Non-malignant liver tissues demonstrated variable MHC antigen expression. Malignant hepatocytes isolated from resected HCC specimens as well as non-tumorous hepatocytes from these HCC specimens also disclosed various degrees of MHC antigen expression. Although we were not able to demonstrate a clear correlation between clinical outcome and MHC antigen expression in HCC, we conclude that the expression of MHC antigens on human hepatocytes and hepatoma cells can be accurately detected by flow cytometry using hepatocyte-specific MAb for selective gating and MHC-specific MAbs. Of note, two cases of non-malignant fetal liver tissues indicated that >95% of fetal hepatocytes expressed class I MHC antigens and <25% of fetal hepatocytes expressed class II MHC antigens. These findings may lead to further investigations into the progression of HCC cells or into the possible mechanisms of the hepatocellular carcinogenesis.

Antibodies, Monoclonal↗

PubMed1997

Negative regulation of a heterologous promoter by human cytomegalovirus immediate-early protein IE2.

The HCMV IE2 protein promiscuously activates transcription of many viral and cellular genes. IE2 also negatively autoregulates its own expression by binding to a strategically positioned IE2 binding site, called CRS, located immediately downstream of the TATA box of the HCMV major IE promoter. Here we show that IE2 is able to repress transcription driven by a heterologous promoter, RSV LTR. Repression of RSV LTR by IE2 is completely dependent of DNA sequences downstream of the TATA box of RSV LTR. A DNA sequence, 5'-CGATACAATAAACG-3', evidently matching the proposed CRS consensus sequence, is located between nucleotides -13 and +1 (relative to the transcription start site) of RSV LTR. Three lines of evidence support the notion that this RSV CRS element is involved in the IE2-mediated repression of RSV LTR. First, introduction of mutation to the RSV CRS element renders to the mutant RSV LTR resistance to IE2-mediated repression. Second, a mutant IE2 defective in DNA binding cannot downregulate transcription from RSV LTR. Third, IE2 specifically binds to the wild-type, but not the mutant, RSV CRS element in vitro. These data, in conjunction with previous works, demonstrate that IE2 can passively repress transcription of homologous and heterologous promoters that contain a CRS element.

Cell Line↗

PubMed1997

Genomic deletion and p53 inactivation in cervical carcinoma.

The tumor-suppressor gene p53 acts as "the guardian of the genome", sensing DNA damage and initiating protective responses. To examine the hypothesis that p53 abnormality leads to increased genomic alterations in primary tumor cells, our study utilized 51 primary tumors of cervical carcinoma and 10 microsatellite markers. These markers were mapped to the short arms of chromosomes 3 and 5, covering the regions 3p13-25 and 5p15.1-15.3. Genomic deletion on 3p and 5p was correlated with genetic or epigenetic p53 inactivation pathways, including p53 mutation, genetic deletion of p53 and cervical infection with human papillomavirus. The proportion of abnormal p53 was found to be significantly higher in the cases exhibiting loss of heterozygosity (LOH) on 5p (p < 0.001), supporting the hypothesis of the presence of a p53-dependent pathway to cervical tumorigenesis. In contrast, however, LOH on 3p was found to be independent of p53 inactivation. A common deletion region, 3p22-24, was identified in 44% of informative cases, and genomic loss at this specific region was correlated with early tumorigenic onset and poor grade of tumor differentiation. Diversity within the patterns of genomic alteration in the same form of cancer suggests different sets of risk/tumorigenic profiles, molecular pathogenesis, as well as prognosis and outcome.

Adult↗