Biomedical subjects

W P Wang

Publications and source records attributed to W P Wang.

At least 19 recordsLinked to original sources

PubMed2001

Inhibition of proteasome function induced apoptosis in gastric cancer.

The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21(waf1) and p27(kip1) at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G(1) phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer.

Adenocarcinoma↗

PubMed2001

Seasonality of growth in Shanghai infants (n=4128) born in 11 consecutive years.

OBJECTIVE: To describe the seasonal growth patterns in Shanghai infants, to explore seasonal time lag between weight gain and length gain, and to investigate the long-term effect of birth season on early postnatal growth. DESIGN: Community-based longitudinal study. SETTING: Shanghai, People's Republic of China. METHOD: Children were followed up monthly from 1 to 6 months, 3 monthly from 6 to 12 months, and 6 monthly from 12 to 24 months. SUBJECTS: A total of 6018 children born between 1 January 1980 and 31 December 1990. MAIN OUTCOME MEASURES: Weight gain, length gain and change in body mass index (BMI) over the seasons of the year. RESULTS: The infants tended to grow faster in height in spring and summer, and faster in weight and BMI in autumn and winter. The seasonal effect on weight gain and length gain is largely independent. The mean length value at 1 month of age was about 2.0 cm higher in infants born in May to July than in those born in November to February. At 24 months of age this difference was reduced to about 0.7 cm. CONCLUSIONS: There is a clear and consistent seasonality in growth in Shanghai infants. The seasonality seems to act independently on weight and length. Birth month has some association with attained size, but this is reduced during the first 2 y of life.

Body Height↗

PubMed2001

Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication.

BACKGROUND: Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication. METHODS: The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression. RESULTS: Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication. CONCLUSIONS: Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.

Adolescent↗

PubMed2001

Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways.

BACKGROUND AND AIMS: Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved. METHODS: Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies. RESULTS: Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production. CONCLUSIONS: Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.

Adenocarcinoma↗

PubMed2001

12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.

Arachidonic acid release from membrane phospholipids is essential for tumour cell proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism. The present study investigated the expression of 12-lipoxygenase and its effect on cell proliferation as well as survival in two human gastric cancer cell lines (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric cancer cell lines. The biochemical characteristics of apoptosis were p53-independent combined with a decrease in bcl-2 expression. Caspase-7 was proteolytically activated and responsible for the apoptosis execution.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2001

Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats.

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. The present study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced colitis in rats and analyzed the severity of colitis along with altered HO activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also assayed. HO activity and HO-1 gene expression increased markedly after TNBS induction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP also enhanced reactive oxygen species and iNOS expression, both of which were dramatically increased after the TNBS enema. L-Arginine pretreatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects probably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.

Animals↗

PubMed2001

Inducible HSP70 mediates delayed cardioprotection via U-50488H pretreatment in rat ventricular myocytes.

To test the hypothesis that heat-shock proteins (HSPs) mediate delayed cardioprotection of prior kappa-opioid receptor (kappa-OR) stimulation, we first correlated cellular injury and viability with the expression of HSP70s in isolated rat ventricular myocytes subjected to prior kappa-OR stimulation with the selective agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H) and delayed lethal simulated ischemia (LSI). Cell injury and viability were indicated by lactate dehydrogenase release and trypan blue exclusion, respectively. The reduced injury and increased viability after pretreatment with U-50488H were concentration dependent and correlated directly with the expression of both stress-inducible (HSP70) and constitutive (HSC70) proteins. The effects mimic those with metabolic inhibition preconditioning (MIP). The cardioprotection against LSI by pretreatment with U-50488H and MIP was abolished and antagonized, respectively, via blockade of the kappa-OR by its selective antagonist, nor-binaltorphimine. We also found that blockade of the production of HSP70 but not HSC70 blocked the inhibitory effect of pretreatment with U-50488H on injury and viability. These observations provide evidence that stress-inducible HSP70 mediates delayed cardioprotection of prior kappa-OR stimulation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2001

Prophylactic total thyroidectomy in an 8-year-old girl with multiple endocrine neoplasia type 2A.

We report a genetic carrier of multiple endocrine neoplasia type 2A (MEN 2A) who underwent prophylactic total thyroidectomy. The asymptomatic carrier of MEN 2A, an 8-year-old Taiwanese girl, was admitted for early thyroidectomy. Preoperative basal plasma concentrations of calcitonin and intact parathyroid hormone, and urine vanillylmandelic acid excretion, were normal. Ultrasonography of the thyroid was also normal. Pathology did not reveal any gross lesion but C-cell hyperplasia of the thyroid gland was found microscopically. Prophylactic total thyroidectomy is encouraged and is justified during the first decade of life for MEN 2A carriers.

Child↗

PubMed2000

Intragastric administration of heparin enhances gastric ulcer healing through a nitric oxide-dependent mechanism in rats.

Our preliminary finding indicated that intravenous (i.v.) injection of heparin increased gastric ulcer healing in rats. However, the anticoagulant action of i.v. heparin could produce complications in ulcer patients if the drug was used as an anti-ulcer agent. The present study aimed to investigate whether intragastric (i.g.) administration of heparin, known to have no anticoagulant activity, would have the similar ulcer healing effect and the relationship of this effect, if any, with nitric oxide (NO), a substance suggested to be important for ulcer healing. Heparin (100, 500, 1000 U/kg, i.g. ) administered once daily for 4 days accelerated the healing of gastric ulcer induced by acetic acid in Sprague-Dawley rats, which was accompanied by an increase in mucosal proliferation and regeneration at the ulcer margin, microvessel number both at the ulcer margin and base, and the thickness of mucus layer. Both activity and content, but not the mRNA of constitutive nitric oxide synthase (cNOS) in the gastric mucosa were enhanced. L-N(G)-nitroarginine methyl ester (L-NAME), an inhibitor of NOS activity blocked the cNOS activity activated by heparin and reversed the beneficial effects of heparin on ulcer healing. The bleeding time was not altered by i.g. heparin. These findings demonstrate that i.g. heparin promotes the healing processes of gastric ulcer. Such effect is suggested to act through the stimulation of mucosal cNOS activity. In addition, i.g. heparin is better than i.v. heparin without the potential anticoagulation effect.

Administration, Oral↗

PubMed2000

Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin.

We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4(+) and CD8(+) T cells and NK (asialoGM1(+) ) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4(+) and CD8(+) T, as well as asialoGM1(+) cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM(+) and IgA(+) B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8(+) cells were significantly increased by treatment with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-gamma presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-gamma and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.

Administration, Oral↗

PubMed2000

The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract.

BACKGROUND: Cigarette smoking was shown to delay gastric ulcer healing and reduce synthesis of mucus, which is important for gastric ulcer protection and healing. Polyamines are important in these processes. AIMS: To study the effects of cigarette smoking on the synthesis of mucus and to investigate if such an effect is acting by interference with the polyamine pathway. METHODS: Gastric mucosal ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer size were determined after different concentrations of cigarette smoke exposure (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and ornithine decarboxylase activity and mRNA expression were also assessed in cigarette smoke extract treated MKN-28 cells. RESULTS: Exposure to cigarette smoke significantly reduced the thickness of the mucous secreting layer and gastric mucosal ornithine decarboxylase activity in animals with or without ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette smoke extract significantly reduced mucus synthesis and ornithine decarboxylase activity but not its mRNA expression in MKN-28 cells. The reduction in mucus synthesis was restored by spermidine. CONCLUSIONS: Cigarette smoke and its extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of ornithine decarboxylase activity in gastric mucosa is closely associated with this effect.

Animals↗

PubMed2000

Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking.

Cigarette smoking is associated with peptic ulcer diseases. Smokers have lower levels of salivary epidermal growth factor (EGF) than nonsmokers. We investigated whether reduction of EGF is involved in the delay of gastric ulcer healing by cigarette smoking. Rats with acetic acid-induced ulcers were exposed to cigarette smoke (0, 2, or 4% vol/vol) 1 day after ulcer induction. EGF level was elevated 1 day after ulcer induction in salivary glands and serum, and 4 days after ulcer induction in the gastric mucosa. However, cigarette smoke depressed these beneficial effects and EGF mRNA expression in salivary glands and gastric mucosa. Cigarette smoke delayed gastric ulcer healing and reduced cell proliferation, angiogenesis, and mucus synthesis. Exogenous EGF (10 and 20 microg/kg i.v.) before smoke exposure reversed the adverse effects of cigarette smoke, whereas vascular endothelial growth factor level and nitric oxide synthase activity were unaffected. It is concluded that the detrimental effect of cigarette smoke on ulcer healing is a consequence of reduction of angiogenesis, cell proliferation, and mucus secretion through the depressive action on EGF biosynthesis and its mRNA expression in salivary glands and gastric mucosa.

Animals↗

PubMed2000

[The role of theophylline in the improvement of scop-induced learning and memory impairment].

Adenosine and ACh contents in hippocampus, striatum region around the nucleus of basal meynert (NBM) and the frontal and temporal parts of rat cortex were measured by a high performance liquid chromotography-electronic detector (HPLC-ECD). Adenosine content in 18~20 month-old rats was significantly higher than that of 3~6 month-old rats, while ACh content in 18~20 month-old rats was lower than that of 3~6 month-old ones. Learning and memory impairment models were established by induction of SD rats with scopolamine (0.5 mg/kg, ip), which were injected with an adenosine receptor antagonist theophylline (1.0 mg/5 microliter, icv), and the step-down test was performed. The error frequency in the step-down test decreased significantly (P<<0.05), and the retention time was longer than that of control. Furthermore, ACh content increased in all the three different brain regions. The above results suggest that adenosine may play an important role in senile learning and memory impairment, and theophylline may improve scopolamine-induced learning and memory impairment by increasing ACh content. In consequence, theophylline could be a promising drug for ameliorating senile learning and memory impairment.

Acetylcholine↗

PubMed1999

Metastatic rat carcinoma cells express a new retrotransposon.

Genes differentially expressed by a rat bladder carcinoma NBT-II cells and their in-vivo-selected metastatic M-NBT-II variant were analysed. Amplification and cloning of a 277-bp B sequence, exclusively expressed by the M-NBT-II cells, were performed, and this sequence was detected as a 6.7-kb RNA. This fragment shares 46-50% identities with the gag-related protein of mouse and hamster Intracisternal A Particles (IAPs). Screening of a M-NBT-II cDNA library with the B probe selected a 1671-bp sequence corresponding to the 5' end of a novel retrotransposon member of the rat IAP family. This sequence has a strong identity with the Ecker Rat IAP (ERA-IAP) except for the B portion and has an open reading frame potentially encoding a 114-amino-acid gag retrovirus-related protein. Rearrangement of this new retrotransposon could be relevant with the tumor progression in our model system since it is only expressed in the M-NBT-II in-vivo-selected carcinoma metastasis.

Amino Acid Sequence↗

PubMed1999

Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats.

BACKGROUND & AIMS: Cigarette smoking is associated with inflammatory bowel diseases (IBDs), particularly Crohn's disease, in humans. The aim of this study was to examine whether passive cigarette smoking aggravates experimental IBD in rats and to clarify the underlying mechanisms. METHODS: Rats were exposed to cigarette smoke (CS) for 1 hour once daily for 4 days before induction of IBD by 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-ethanol enema and were then killed at 2, 6, or 24 hours later. RESULTS: Preexposure to CS significantly potentiated colonic damage induced by TNBS. TNBS-ethanol enema caused a pronounced increase in colonic myeloperoxidase activity, leukotriene B(4) level, and also inducible nitric oxide synthase activity, its protein, and messenger RNA expression. These parameters were all significantly increased further by exposure to CS. In contrast, increased colonic superoxide dismutase activity after TNBS-ethanol enema was attenuated by CS exposure. The potentiating effects of CS exposure on TNBS-induced IBD were significantly alleviated after pretreatment with cyclosporin A (an immunosuppressant), N (G)-nitro-L-arginine methylester (a nitric oxide synthase inhibitor), and dimethyl sulfoxide (a hydroxyl radical scavenger). CONCLUSIONS: The results show that promotion of neutrophil infiltration and free radical production contributed significantly to the potentiating effect of passive cigarette smoking on experimental IBD.

Animals↗

PubMed1999

Cation channel formed at lipid bilayer by Cinnamomin, a new type II ribosome-inactivating protein.

Cinnamomin, a new type II ribosome-inactivating protein, purified from the seeds of Cinnamonum camphora is reconstituted into the membranes of planar lipid bilayer and giant liposome. The channel-forming activity of the cinnamomin is found and cation permeability of the channel is characterized by patch clamp. In an asymmetric solution system, bath 150/pipette 100 mM KCl, the unit conductance is 140+/-7 pS and the reversal potential is 10.4+/-0.6 mV, very close to the theoretical value of the K+ electrode. The results offer an interpretation for internalization of the RIP and the cytotoxicity difference between single and two chain RIP.

Algal Proteins↗

PubMed1999

Msx-2 and the regulation of organ size: epidermal thickness and hair length.

During organogenesis, the issue of size regulation is as important as shape and differentiation. We propose that the regulation of the dimensions of the epithelium and its appendages (length, width, thickness) are based on regulation of cell numbers in specific sites, reflecting the input and output of cells in that region. This process is in turn regulated by the flow from the domain of proliferating cells to the domain of postmitotic differentiated cells. When the homeobox gene Msx-2 is over-expressed in transgenic mice under the control of the CMV promoter, the epidermis is thickened with hyperproliferation and hyperkeratosis. Hairs are shorter and the matrix region is shrunken. We suggest that Msx-2 may be one of the regulators involved in the control of organ size, and the above phenotypes are the manifestations of an increased cellular flow from proliferation domain to differentiation domain in the tissue.

Animals↗

PubMed1998

Genetic analysis of N-acetyltransferase polymorphism in a Chinese population.

AIM: To study the genetic basis of N-acetylatransferase polymorphism in Chinese. METHODS: Genotypes in 120 healthy Han volunteers from 19 provinces of China were assayed. The 3 common mutant alleles (M1, M2, M3) and one normal wild-type (WT) allele of the N-acetyltransferase (NAT2) gene were detected by allele-specific polymerase chain reaction technique. RESULTS: The NAT2 allele frequencies in 120 Chinese (WT = 0.625, M1 = 0.0458, M2 = 0.188, M3 = 0.142) were different (P < 0.01). The NAT2 genotype distribution for all detected combinations of NAT2 alleles in 120 Chinese subjects was consisitent with Hardy-Weinberg equilibrium (chi 2 = 7.27, nu = 8, 0.7 > P > 0.5). Fifty subjects (41.7%) were homozygous wildtypes, 50 subjects (41.7%) were heterozygous mutants, and 20 subjects (16.7%) were homozygous mutants. CONCLUSION: The lower frequency of mutant M1 allele compared with that of Caucasians explains the low frequency of slow acylators in Chinese.

Acetyltransferases↗