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Biomedical subjects

T C Wang

Publications and source records attributed to T C Wang.

At least 73 records · Page 4Linked to original sources
PubMed1998

Synthesis and anticancer evaluation of certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl-gamma-butyrolactones.

Certain gamma-aryloxymethyl-alpha-methylene-gamma-phenyl- gamma-butyrolactones were synthesized and evaluated for their anticancer activity. These compounds demonstrated a strong growth inhibitory activity against leukemia cell lines but are relatively inactive against non-small cell lung cancers and CNS cancers. The anticancer potency for aryl portion is in an order of quinoline > 8-hydroxyquinoline > 2-methylquinoline >> naphthalene >> benzene.

4-Butyrolactone↗
PubMed1998

Close correlation between telomerase expression and adenomatous polyp progression in multistep colorectal carcinogenesis.

To investigate the role of telomerase in the multistep colorectal carcinogenesis, we examined telomerase activity in 31 adenomatous polyps and 22 paired cancer-normal mucosa specimens from non-hereditary nonpolyposis colorectal cancer patients. Telomerase activity was detected in 18% of normal mucosa, 16% of small (<1.0 cm) polyps, 20% of intermediate polyps, 71% of large (>2.0 cm) polyps, and 96% of adenocarcinoma samples (P for trend, <0.0001). High-level enzyme activities were seen in none of the normal mucosa, 5% of small polyps, 20% of intermediate polyps, 43% of large polyps, and 73% of adenocarcinoma samples (P for trend, <0.0001). These data indicate telomerase reactivation occurs with adenomatous polyp progression in multistep colorectal carcinogenesis.

Adenomatous Polyposis Coli↗
PubMed1998

Oxidative stress activates the human histidine decarboxylase promoter in AGS gastric cancer cells.

Oxidant stress is thought to play a role in the pathogenesis of many gastric disorders. We have recently reported that histidine decarboxylase (HDC) promoter activity is stimulated by gastrin through a protein kinase C- and extracellular signal-regulating kinase (ERK)-dependent pathway in gastric cancer (AGS-B) cells, and this transcriptional response is mediated by a downstream cis-acting element, the gastrin response element (GAS-RE). To study the mechanism through which oxidant stress affects gastric cells, we examined the effects of hydrogen peroxide (H2O2) on HDC promoter activity and intracellular signaling in AGS-B cells. H2O2 (10 mM) specifically activated the HDC promoter 10-12-fold, and this activation was blocked by both mannitol and N-acetylcysteine. Hydrogen peroxide treatment of AGS-B cells increased the phosphorylation and kinase activity of ERK-1 and ERK-2, but did not affect Jun kinase tyrosine phosphorylation or kinase activity. In addition, treatment of AGS-B cells with H2O2 resulted in increased c-fos/c-jun mRNA expression and AP-1 activity, and also led to increased phosphorylation of epidermal growth factor receptor (EGFR) and Shc. H2O2-dependent stimulation of HDC promoter activity was completely inhibited by kinase-deficient ERKs, dominant-negative (N17 and N15) Ras, and dominant-negative Raf, and partially blocked by a dominant-negative EGFR mutant. In contrast, protein kinase C blockade did not inhibit H2O2-dependent induction of the HDC promoter. Finally, deletion analysis demonstrated that the H2O2 response element could be mapped to the GAS-RE (nucleotides 2 to 24) of the basal HDC promoter. Overall, these studies suggest that oxidant stress activates the HDC promoter through the GAS-RE, and through an Ras-, Raf-, and ERK-dependent pathway at least partially involving the EGFR.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Possible role of telomerase activation in the cancer predisposition of patients with hereditary nonpolyposis colorectal cancers.

BACKGROUND: Hereditary nonpolyposis colorectal cancer syndrome (HNPCC syndrome; also called Lynch syndrome) is one of the most common cancer predisposition syndromes. Most cases of cancer associated with this syndrome are due to the inheritance of germline mutations in genes that encode proteins required for DNA mismatch repair; defects in these proteins allow mutations to accumulate more rapidly in the DNA and influence the rate of cancer development. Recent studies indicate that the reactivation of the activity of telomerase, an enzyme involved in the synthesis of chromosomal ends, in somatic cells may play a role in carcinogenesis. In this study, we evaluated the expression of telomerase in normal and cancerous colorectal tissue specimens from HNPCC and non-HNPCC patients. METHODS: The polymerase chain reaction-based telomeric repeat amplification protocol was used to assay telomerase activity in colorectal tissue specimens from 33 non-HNPCC patients (23 normal, 26 polyps, and 37 cancer specimens) and from 24 HNPCC patients (24 normal, 0 polyps, and 28 cancer specimens). RESULTS: Thirty-one of 37 carcinoma samples from 18 non-HNPCC patients and 27 of 28 carcinoma samples from 24 HNPCC patients were found to be positive for telomerase activity. Whereas only one of 23 normal mucosa samples from 23 non-HNPCC patients was found to have (weak) telomerase activity, eight of 24 normal mucosa samples from 24 HNPCC patients were positive for telomerase; the difference between the two groups was statistically significant (two-sided P = .0226). IMPLICATION: This study generates the hypothesis that genetic defects in individuals with HNPCC syndrome facilitate the reactivation of telomerase activity, a process which may be associated with their predisposition to develop cancer.

Adult↗
PubMed1998

Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection.

BACKGROUND & AIMS: Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis that may progress to atrophic gastritis, a premalignant process. A mouse model of Helicobacter felis infection was used to study possible genetic determinants of the response to infection. METHODS: Three inbred mouse strains with known secretory phospholipase A2 (sPLA2) genotypes [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (-/-)] were orally infected with H. felis and examined longitudinally using routine histology, immunocytochemistry, electron microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies. RESULTS: Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide. In contrast, no significant change in these cell types was observed in BALB/c and C3H/HeJ strains. Increased expression of sPLA2 was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA2 expression was absent in C57BL/6 mice. CONCLUSIONS: H. felis infection leads to increased apoptosis and altered cellular differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA2 expression. Because sPLA2 has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp formation in the colon, these studies suggest that sPLA2 may also influence the gastric epithelial response to Helicobacter infection.

Animals↗
PubMed1998

Telomerase activity in benign and malignant human thyroid tissues.

Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomerase repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity plays a role in carcinogenesis and immortalization. In this work, the status of telomerase activity during the development of human thyroid cancer was determined using telomeric repeat amplification protocol (TRAP) in 14 nodular hyperplasia, 14 adenomas, 23 papillary carcinomas and 11 follicular carcinomas. Positive telomerase activity was detected in 2 of 14 nodular hyperplasias (14%), 4 of 14 adenomas (29%), 12 of 23 papillary carcinomas (52%) and 10 of 11 follicular carcinomas (91%). The cancers that are negative for telomerase activity are mostly in early stage (stage I or II). These results suggest that telomerase reactivation plays a role during the development of thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1998

Vacuolating toxin gene polymorphism among Helicobacter pylori clinical isolates and its association with m1, m2, or chimeric vacA middle types.

BACKGROUND: Helicobacter pylori vacuolating cytotoxin encoded by vacA plays an essential role in H. pylori-related pathogenesis. Specific vacA alleles are believed to be associated with increased virulence. Association among vacA polymorphism, vacA middle genotypes, and various H. pylori-related diseases was thus investigated. METHODS: Eighty-nine isolates from patients with various gastrointestinal diseases were examined for restriction fragment length polymorphism (RFLP) of the 2.0-kb polymerase chain reaction-amplified vacA middle region. Further genetic heterogeneity was assessed with ureA-ureB RFLP. RESULTS: Twenty-eight distinct vacA RFLPs were seen among 89 isolates. Each pattern was associated with one specific vacA middle genotype. The association of specific RFLPs with certain clinical manifestations was noted among six common groups. Further RFLP analysis of the 2.4-kb ureA-ureB segment from isolates in four popular vacA RFLPs showed high genetic variation. CONCLUSIONS: The vacA genetic polymorphism may be associated with different gastrointestinal diseases.

Bacterial Proteins↗
PubMed1998

Endozepine stupor. Recurring stupor linked to endozepine-4 accumulation.

Recurring stupor can be caused by repeated metabolic, toxic or structural brain disturbances. Recently, cases of recurring stupor, with fast EEG activity were shown to display increased endogenous benzodiazepine-like activity during the episodes of stupor. Patients with recurring stupor underwent extensive metabolic and toxicologic screening, EEG and brain imaging. Endozepines and exogenously administered benzodiazepines were assayed in plasma and CSF by means of mass spectrometry. Flumazenil, a benzodiazepine antagonist was administered and the behavioural and EEG responses monitored. Treatment with oral flumazenil was attempted in selected cases. Twenty patients were found with recurring stupor. Episodes had begun between ages 18 and 67 years, and in nine patients, had disappeared spontaneously after 4-6 years with symptoms. Stupor lasted hours or days. Onset of the episodes and frequency were unpredictable. Patients were normal between attacks. Stupor was characterized by initial drowsiness, staggering and behavioural changes, followed by deep sleep and spontaneous recovery with post-ictal amnesia. Biochemical screening and brain imaging were always normal. Ictal EEG showed fast background activity, and flumazenil transiently awoke the patients and normalized the EEG. In the nine cases examined, endozepine-4 levels were increased during the stupor. Oral flumazenil reduced the frequency of the attacks in three of these nine patients. Recurring episodes of stupor may be due to increased endozepine-4. We propose the term 'endozepine stupor' for such episodes. Endozepine-4 is an endogenous ligand for the benzodiazepine recognition site at the GABAA receptor, with unknown molecular structure.

Adult↗
PubMed1998

Genotoxicity of propoxur and its N-nitroso derivative in mammalian cells.

N-Nitroso propoxur (NP) can be synthesized from a widely used N-methylcarbamate insecticide, propoxur, in vitro in the laboratory. Because of the extensive use of aerosol propoxur, the adverse effect on cells of respiratory origin is worth elucidating. In this report, two mammalian cell cultures from respiratory tissues [a hamster lung fibroblast, V79, and a primary rat tracheal epithelial cell (RTE)], were used to investigate the genotoxicity of propoxur and NP. NP was more cytotoxic than propoxur, with LC50s (20 and six times smaller, respectively in V79 and RTE cells. NP significantly induced sister chromatid exchange (> or = 0.01 microg/ml), chromosome aberration (> or = 2.5 microg/ml) and hprt gene mutation (> or = 0.5 microg/ml) in V79 cells, and cell transformation (> or = 0.2 microg/ml) in RTE cells. Results of chromosome aberration and hprt gene mutation indicated that the major pre-mutagenic lesion induced by NP must be the O6-methylguanine adduct, which frequently mispairs with thymine and thus gives rise to a GC-->AT transition. Propoxur was not mutagenic to either type of cells. However, it inhibited gap-junctional intercellular communication in V79 cells, which indicates that propoxur could act through some epigenetic mechanisms, such as tumor promotion or cell proliferation, in the multiple process of chemical carcinogenesis.

Animals↗
PubMed1998

Genetic toxicity of N-methylcarbamate insecticides and their N-nitroso derivatives.

N-Methylcarbamate esters are an important group of insecticides. They have lower acute toxicity to vertebrates than organophosphates, although their genotoxicity has not been adequately studied. Here we investigate the cytotoxicity and genotoxicity of N-methylcarbamate insecticides and their N-nitroso derivatives in Chinese hamster V79 cells, using the hprt locus as a marker, and also assess inhibition of gap junctional intercellular communication. N-Methylcarbamate insecticides were chemically N-nitrosated to obtain the N-nitroso derivatives. N-Nitrosation greatly increased the cytotoxicity and mutagenicity of N-methylcarbamates at the hprt locus in Chinese hamster V79 cells. The mutagenic potential of N-nitroso-N-methylcarbamates was much higher than those of many other known mutagenic nitroso compounds, as well as some non-nitroso mutagenic alkylating agents. Parental N-methylcarbamates themselves were not mutagenic, however, they inhibited gap junctional intercellular communication half as effectively as the well-studied tumor promoter 12-O-tetradecanoylphorbol-13-acetate. The findings show that N-methylcarbamate insecticides and their N-nitroso derivatives have the potential to act through mediation of epigenetic and genotoxic mechanisms respectively in the multiple stages of chemical carcinogenesis.

Aldicarb↗
PubMed1998

Detection of microcalcifications in digital mammograms using wavelets.

This paper presents an approach for detecting microcalcifications in digital mammograms employing wavelet-based subband image decomposition. The microcalcifications appear in small clusters of few pixels with relatively high intensity compared with their neighboring pixels. These image features can be preserved by a detection system that employs a suitable image transform which can localize the signal characteristics in the original and the transform domain. Given that the microcalcifications correspond to high-frequency components of the image spectrum, detection of microcalcifications is achieved by decomposing the mammograms into different frequency subbands, suppressing the low-frequency subband, and, finally, reconstructing the mammogram from the subbands containing only high frequencies. Preliminary experiments indicate that further studies are needed to investigate the potential of wavelet-based subband image decomposition as a tool for detecting microcalcifications in digital mammograms.

Breast Neoplasms↗
PubMed1998

Involvement of recF, recO, and recR genes in UV-radiation mutagenesis of Escherichia coli.

The recF, recO, and recR genes were originally identified as those affecting the RecF pathway of recombination in Escherichia coli cells. Several lines of evidence suggest that the recF, recO, and recR genes function at the same step of recombination and postreplication repair. In this work, we report that null mutations in recF, recO, or recR greatly reduce UV-radiation mutagenesis (UVM) in an assay for reversion from a Trp- (trpE65) to a Trp+ phenotypes. Introduction of the defective lexA51 mutation [lexA51(Def)] and/or UmuD' into recF, recO, and recR mutants failed to restore normal UVM in the mutants. On the other hand, the presence of recA2020, a suppressor mutation for recF, recO, and recR mutations, restored normal UVM in recF, recO, and recR mutants. These results indicate an involvement of the recF, recO, and recR genes and their products in UVM, possibly by affecting the third role of RecA in UVM.

Bacterial Proteins↗
PubMed1998

alpha-Methylene-gamma-butyrolactones: synthesis and vasorelaxing activity assay of coumarin, naphthalene, and quinoline derivatives.

Certain alpha-methylene-gamma-butyrolactone derivatives of coumarin, naphthalene, and quinoline were synthesized and evaluated for vasorelaxing effects on isolated rat thoracic aorta. The 7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2H- 1- benzopyran-2-ones, which have an aliphatic methyl substituent at the lactone C2, were more active than their C2-phenyl counterparts against high-K+ (80 mM) medium, Ca2+ (1.9 mM)-induced vasoconstriction and the norepinephrine (NE, 3 microM)-induced phasic and tonic constrictions (2a vs. 2b; 2c vs. 2d; 2e vs. 2f; 2g vs. 2h). Although 3-chloro-7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2- furanyl)methoxy]-4-methyl-2H-1-benzopyran-2-one (2g) demonstrated the most potent inhibitory activities on the NE-induced phasic and tonic constrictions at concentrations of as low as 10 micrograms/ml, it possesses both affinity for NE-receptor and intrinsic activity to trigger the vasoconstriction. However, 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2- furanyl)methoxy]quinoline (10a) and other quinoline derivatives (11a, 12a) are pure irreversible non-competitive blockers of NE-receptor with no intrinsic activity. The aromatic ring played an important role in the vasorelaxing effects of alpha-methylene-gamma-butyrolactones; naphthalene was inactive, quinolines exhibited only affinity to the alpha-receptor, and coumarins possessed both affinity and intrinsic activity.

4-Butyrolactone↗
PubMed1998

Magnetic resonance angiography in the diagnosis of thoracic venous obstruction.

The aims of this study were to evaluate the diagnostic value of orthogonal magnetic resonance angiography (MRA) and to compare the results of MRA with those of digital subtraction venography (DSV) in thoracic venous diseases. Ten normal volunteers were evaluated using two-dimensional time-of-flight MRA in three orthogonal planes to determine the image quality of each venous segment. Twelve consecutive patients suspected of having thoracic venous disease were studied with both MRA and DSV. In the normal subjects, the plane perpendicular to the target vein provided the most consistent visualization. Using three orthogonal MRA images, a diagnostic-quality image was obtained in 175 (83%) of 210 venous segments in normal volunteers. In patients with thoracic venous obstructive disease, MRA was more effective than DSV in detecting total (84 vs 54), patent (56 vs 36), stenotic (13 vs 10), and obstructive (15 vs 8) venous segments, poststenotic or postobstructive veins (15 vs 10), thrombosis of the internal jugular vein (7 vs 2), intraluminal thrombus (5 vs 3), and azygos veins (12 vs 2). Using venous segments visible on DVS (n = 54) as the standard, the sensitivity and specificity of MRA were 94% and 100%, respectively, in detecting venous patency, and 100% and 98% in detecting complete venous obstruction. In the shoulder region, the sensitivity and specificity of MRA were 93% and 100%, respectively, in detecting venous patency, and 100% and 97% in detecting venous obstruction. We conclude that MRA with three orthogonal planes can provide relatively complete and reliable venous mapping, without the need for contrast medium.

Adult↗
PubMed1997

Inhibition of telomerase activity by PKC inhibitors in human nasopharyngeal cancer cells in culture.

Telomerase is a specialized ribonucleoprotein polymerase that adds hexanucleotides (TTAGGG) onto human chromosomal ends. The expression of telomerase activity has been associated with cell immortalization and the malignant phenotype in most cancers. How the telomerase activity is regulated in cancer cells is presently not known. In this work, the effects of cell cycle blockers, DNA damaging agents, TopII inhibitors and proteins kinase inhibitors on the telomerase activity were examined in cultured nasopharyngeal carcinoma cells NPC-076. Agents which interfere with tubulin assembly (Taxol and vinblastine) and agents which arrest cells at S phase (methotrexate and 5-fluorouracil) did not inhibit telomerase activity of treated cells. Agents which damage DNA (cisplatin, methyl methanesulfonate, and UV radiation) and TopII inhibitors (etoposide and daunorubicin) also did not inhibit telomerase activity of treated cells. Among the protein kinase inhibitors examined, no significant inhibition of telomerase activity was observed with cells treated with quercetin, H-89, or herbimycin A. On the other hand, two protein kinase C (PKC) inhibitors (bisindolylmaleimide I and H-7) were found to produce a big inhibition of telomerase activity in treated cells. Staurosporine produced a moderate inhibition, and sphingosine had a small inhibitory effect. The inhibition of telomerase activity by PKC inhibitors appears to be specific since the treated cells were mostly viable (i.e., greater than 75%) and still retained significant levels of protein synthesis capability. These results implicate that protein kinase C is involved in the regulation of telomerase activity in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗