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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 163 records · Page 9Linked to original sources
PubMed2004

Protein kinase A and calcium/calmodulin-dependent protein kinase II regulate glycine and GABA release in auditory brain stem nuclei.

We reported previously that unilateral cochlear ablation (UCA) in young adult guinea pigs induced protein kinase C (PKC)-dependent plastic changes in the electrically evoked release of exogenous [14C]glycine ([14C]Gly) or [14C]-gamma-aminobutyric acid ([14C]GABA) in several brain stem auditory nuclei. The present study assessed whether such changes depended on protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII). In the major subdivisions of the cochlear nucleus (CN) and the main nuclei of the superior olivary complex (SOC) dissected from intact animals, dibutyryl-cyclic adenosine monophosphate (DBcAMP) (0.2 mM), a PKA activator, elevated release by 1.6-2.3-fold. The PKA inhibitor, H-89 (2 microM), did not alter the release but blocked the stimulatory effects of DBcAMP. These findings suggested that PKA could positively regulate glycinergic and GABAergic release. After UCA, PKA regulation declined and failed in the ventral CN but persisted in the SOC nuclei. After 145 postablation days, H-89 reversed elevations of [14C]GABA release in the medial nucleus of the trapezoid body (MNTB). A CaMKII inhibitor, KN-93, reversed depressions of [14C]Gly release in the DCN. Thus, the postablation plasticities in these nuclei probably depended on PKA or CaMKII. Both H-89 and KN-93 depressed [14C]Gly release in the lateral superior olive (LSO) and ipsilateral medial superior olive (MSO), suggesting that either kinase was used by endogenous mechanisms in these nuclei to upregulate glycinergic release. In contrast, KN-93 elevated [14C]GABA release in the contralateral MNTB, suggesting a downregulatory action of CaMKII, an action opposite to that of PKA.

Animals↗
PubMed2004

Genome-wide analysis of defense-responsive genes in bacterial blight resistance of rice mediated by the recessive R gene xa13.

Defense responses triggered by dominant and recessive disease resistance (R) genes are presumed to be regulated by different molecular mechanisms. In order to characterize the genes activated in defense responses against bacterial blight mediated by the recessive R gene xa13, two pathogen-induced subtraction cDNA libraries were constructed using the resistant rice line IRBB13--which carries xa13--and its susceptible, near-isogenic, parental line IR24. Clustering analysis of expressed sequence tags (ESTs) identified 702 unique expressed sequences as being involved in the defense responses triggered by xa13; 16% of these are new rice ESTs. These sequences define 702 genes, putatively encoding a wide range of products, including defense-responsive genes commonly involved in different host-pathogen interactions, genes that have not previously been reported to be associated with pathogen-induced defense responses, and genes (38%) with no homology to previously described functional genes. In addition, R-like genes putatively encoding nucleotide-binding site/leucine rich repeat (NBS-LRR) and LRR receptor kinase proteins were observed to be induced in the disease resistance activated by xa13. A total of 568 defense-responsive ESTs were mapped to 588 loci on the rice molecular linkage map through bioinformatic analysis. About 48% of the mapped ESTs co-localized with quantitative trait loci (QTLs) for resistance to various rice diseases, including bacterial blight, rice blast, sheath blight and yellow mottle virus. Furthermore, some defense-responsive sequences were conserved at similar locations on different chromosomes. These results reveal the complexity of xa13-mediated resistance. The information obtained in this study provides a large source of candidate genes for understanding the molecular bases of defense responses activated by recessive R genes and of quantitative disease resistance.

Chromosomes, Plant↗
PubMed2004

Thermally tunable narrow-bandpass filter based on a linearly chirped fiber Bragg grating.

We propose a new method for the development of a tunable optical bandpass filter (TOBF) based on a linearly chirped fiber Bragg grating (LCFBG). A NiCr wire heater is used to heat the LCFBG at a small point to introduce a narrow passband within the stop band of the LCFBG. The central wavelength of the passband is tuned by scanning the wire heater along the LCFBG. As an example demonstrating the effectiveness of the proposed method, we demonstrate a TOBF with a very small 3-dB bandwidth of approximately 7 pm, a tuning range of 16.4 nm, and a rejection ratio of more than 25 dB. Compared with previously reported tunable-fiber-based bandpass filters, this method provides the advantages of a large tuning range, continuous tunability, a switchable passband, a simple tuning mechanism, low cost, and narrow bandwidth.

Journal Article↗
PubMed2004

Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.

BACKGROUND: Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects Res B 71:55-68 (this issue), 2004] with exposure on gestation days (GD) 6-17 (rat), 6-18 (rabbit) or 6-15 (mouse) showed that only IVL984 treatment resulted in embryo lethality and cardiac defects. Objectives of the current study were to determine the critical period for inducing IVL984-related embryo-fetal effects, and to test the hypothesis that these effects were due to higher embryo drug concentrations. METHODS: IVL984 was administered at 40 mg/kg/day to pregnant rats on GD 4 and 5, GD 6 and 7, GD 8 and 9, GD 10 and 11, or GD 12 and 13. Animals were euthanized on GD 21 and uteri and fetuses were examined. A treatment period of GD 10-12 was selected for subsequent toxicokinetic (TK) studies in which IVL984, HMR1031, or IVL745 was administered to pregnant rats and rabbits. On GD 12, maternal plasma, extra-embryonic tissue (placenta and amniotic fluid), and embryonic tissue were collected and analyzed for drug concentrations. RESULTS: In the IVL984 critical period study in pregnant rats, treatment on GD 10 and 11 resulted in increased post-implantation loss, skeletal variations, and spiral septal defects similar to those observed in standard embryo-fetal development studies with treatment throughout organogenesis. There were no embryo-fetal effects after treatment on GD 4 and 5, GD 6 and 7, or GD 8 and 9. There was a single aorta malformation after treatment on GD 12 and 13. In the TK studies, IVL745, HMR1031, and IVL984 were all detectable in embryonic tissue and there was no evidence for accumulation. Rat and rabbit embryo exposures (AUC or dose-adjusted AUC) on GD 12 could not explain the observed teratology (IVL984<HMR1031<IVL745). Further analyses incorporating pharmacological activity, clearance, and protein binding data provided a positive correlation between embryonic exposure and teratogenic potency. CONCLUSIONS: The critical period for IVL984 in the rat, GD 10 to 11, corresponds to the expression of alpha-4 integrin on the chorion and VCAM-1 on the allantois and myocardium as well as chorioallantoic fusion and formation of the spiral septum. Embryo drug levels adjusted for pharmacological activity, clearance, and protein binding provide a possible explanation for the differing teratogenic potency of IVL984, HMR1031, and IVL745.

Abnormalities, Drug-Induced↗
PubMed2004

The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft.

Osteoprotegerin (OPG) plays a central role in controlling bone resorption. Exogenous administration of OPG has been shown to be effective in preventing osteolysis and limiting the growth of osteolytic metastasis. The objective of this study was to investigate the effects of OPG on osteoblastic prostate cancer (CaP) metastases in an animal model. LuCaP 23.1 cells were injected intra-tibially and Fc-OPG (6.0 mg/kg) was administered subcutaneously three times a week starting either 24 hours prior to cell injection (prevention regimen) or at 4 weeks post-injection (treatment regimen). Changes in bone mineral density at the tumor site were determined by dual x-ray absorptiometry. Tumor growth was monitored by evaluating serum prostate specific antigen (PSA). Fc-OPG did not inhibit establishment of osteoblastic bone lesions of LuCaP 23.1, but it decreased growth of the tumor cells, as determined by decreases in serum PSA levels of 73.0 +/- 44.3% (P < 0.001) and 78.3 +/- 25.3% (P < 0.001) under the treatment and prevention regimens, respectively, compared to the untreated tumor-bearing animals. Administration of Fc-OPG decreased the proliferative index by 35.0% (P = 0.1838) in the treatment group, and 75.2% (P = 0.0358) in the prevention group. The results of this study suggest a potential role for OPG in the treatment of established osteoblastic CaP bone metastases.

Animals↗
PubMed2004

Germline mutational analysis of CDH1 and pathologic features in familial cancer syndrome with diffuse gastric cancer/breast cancer proband in a Chinese family.

AIMS: Hereditary non-polyposis colorectal cancer, thyroid medullary carcinoma, breast/ovarian cancer and gastric cancer/breast cancer syndrome are encountered in surgery. Some gastric cancer/breast cancer syndrome may be the result of a CDH1 germline mutation. This is the first report of CDH1 germline mutations gastric cancer/breast cancer syndrome in Chinese patients. METHODS: Peripheral blood from the proband, as well as, her first and second degree relatives was collected and CDH1 gene exon 1-16 mutations were screened. E-cadherin/beta-catenin proteins expression and histopathologic features were examined on gastric cancer/breast cancer tissues from the proband. RESULTS: A C-->T nucleotide substitution at exon 13 (mRNA 2200 locus, Accession number NM-004360) was found. This was a transition from GCC-->GCT in DNA sequence (Ala154Ala). Diffuse-type gastric cancer and infiltrating ductal breast carcinoma were present. Both tumours preserved E-cadherin/beta-catenin expression immunohistochemically. CONCLUSIONS: Familial cancer syndrome with diffuse-type gastric cancer/breast cancer proband in Chinese has a propensity of early onset during lifespan. No truncating or splice-site CDH1 mutations had been identified in this family. A silent nucleotide variation in exon 13 of the CDH1 gene may contribute to some forms of cancer susceptibility.

Adult↗
PubMed2004

Acute mesenteric venous thrombosis: a better outcome achieved through improved imaging techniques and a changed policy of clinical management.

OBJECTIVE: To analyse and compare the results obtained from acute mesenteric venous thrombosis (MVT) patients before and after the change of the clinical management principle, to assess the factors responsible for the recent better outcome and determine the best management for this disease. MATERIALS AND METHODS: We retrospectively reviewed 41 patients treated for acute MVT admitted in our hospital between 1978 and 2003. Before 1995 (Group I), our policy was to perform surgery in patients with suspected acute MVT. After 1995 (Group II), we changed our policy to a medical approach when achievable. Each patient in this study was assessed for diagnosis, initial management (operative or non-operative), mortality, duration of hospitalisation, and outcome. RESULTS: There were 13 in Group I, 28 in Group II. The mean duration of diagnoses made after admission was 7.3 S.D. 2.6 days for patients in Group I, and 1.5 S.D. 1.2 days for those in Group II (p<0.01, Student's t-test). Eleven patients underwent operations and two patients received non-operative treatment initially in group I, the mortality was 39%; while nine patients underwent operations and 19 patients received non-operative management in group II, the mortality was 11% (p<0.05). No death occurred in the patients with initial non-operative management. The mean duration of hospitalisation was 26 S.D. 6.8 days in Group I and 12.6 S.D. 4.6 days in Group II (p<0.01, Student's t-test). No significant difference in 2-year survival rate between the two groups. CONCLUSION: Recent improvements in imaging techniques and better understanding of the aetiology have led to a dramatic change in the principle and policy of clinical management for acute MVT, which leads to a more favourable outcome of acute MVT.

Acute Disease↗
PubMed2004

Endometrial thickness after misoprostol use for early pregnancy failure.

OBJECTIVES: To assess if there was any potential relationship between endometrial thickness and final treatment outcome in women successfully treated with misoprostol for a first trimester anembryonic gestation, embryonic demise or fetal demise. METHODS: Eighty women were treated with up to two doses of misoprostol 800 microg vaginally for early pregnancy failure. Subjects were scheduled to return 2 (range 1-4), 7 (range 5-9) and 14 (range 12-17) days after treatment. Transvaginal ultrasonography was performed at each follow-up visit. RESULTS: The median endometrial thickness at each of the follow-up visits for women who had expelled the gestational sac was 14 mm, 10 mm, and 7 mm, respectively. The endometrial thickness at the first follow-up visit exceeded 15 mm in 20 subjects (36%) and 30 mm in four subjects (7%). Only three women had a suction aspiration for bleeding after documented expulsion. The endometrial thickness for these women was 11, 13, and 14 mm at the first follow-up visit. CONCLUSIONS: There is no obvious relationship between increasing endometrial thickness and the need for surgical intervention in women treated with misoprostol for early pregnancy failure.

Abortifacient Agents, Nonsteroidal↗
PubMed2004

Automated distal coronary bypass with a novel magnetic coupler (MVP system).

OBJECTIVE: We sought to assess the feasibility of performing sutureless distal coronary artery bypass anastomoses with a novel magnetic coupling device. METHODS: From May 2000 to April 2001, single-vessel side-to-side coronary artery bypass grafting on a beating heart was performed in 39 domestic white pigs (35-60 kg) without the use of mechanical stabilization, shunts, or perfusion bridges. Animals were divided into 2 groups. Seventeen pigs underwent right internal thoracic artery to right coronary artery bypass grafting through a median sternotomy (group 1) with a novel magnetic vascular positioning system (MVP system; Ventrica, Inc, Fremont, Calif). Twenty-two pigs underwent left internal thoracic artery to left anterior descending artery grafting with the MVP anastomotic device through a left anterior minithoracotomy (group 2). This system consists of 2 pairs of elliptical magnetic implants and a deployment device. One pair of magnets forms the anastomotic docking port within the graft; the other pair forms an identical anastomotic docking port within the target vessel. The anastomosis is created when the 2 docking ports magnetically couple. Anastomotic patency was evaluated by means of angiography during the first postoperative week and at 1 month. Histologic studies were performed at different time points as late as 6 months. RESULTS: Right internal thoracic artery to right coronary artery anastomoses and left internal thoracic artery to left anterior descending artery anastomoses were successfully performed with the system in all animals. The self-adherent and self-aligning properties of the implants allowed for immediate and secure approximation of the arteries (total anastomotic time between 2-3 minutes). Anastomoses were constructed without a stabilization platform. Five nondevice-related deaths occurred postoperatively. One-week angiography, performed in 35 surviving animals, showed a patent graft and anastomosis in all cases. The patency rate at 1 month was 97% (33/34). Histologic studies as late as 6 months demonstrated neointimal coverage of the magnets without any significant luminal obstruction. Histology also confirmed the presence of viable tissue between magnets. CONCLUSION: The MVP anastomotic system uses magnetic force to create rapid and secure distal coronary artery anastomoses, which might facilitate minimally invasive and totally endoscopic coronary artery bypass surgery.

Anastomosis, Surgical↗
PubMed2004

Proteasomal inhibition induced by manganese ethylene-bis-dithiocarbamate: relevance to Parkinson's disease.

Maneb, a widely used fungicide, has been associated with Parkinsonism in humans. In experimental models, maneb and its major active element, manganese ethylene-bis-dithiocarbamate (Mn-EBDC) cause selective nigrostriatal neurodegeneration in mice and in rats, respectively. To investigate the mechanisms underlying this neurodegeneration, we studied the effects of Mn-EBDC on proteasomal function, which is decreased in patients with Parkinson's disease (PD), in a dopaminergic neuronal cell line (MES 23.5 or MES). The results demonstrated that exposure of MES cells to 6 microM Mn-EBDC for 7 days produced not only significant neurotoxicity but also inhibition of proteasomal chymotrypsin-like and postglutamyl peptidase activities. Proteasomal dysfunction was accompanied by formation of cytoplasmic inclusions that were positive for alpha-synuclein immunostaining and significantly increased sodium dodecyl sulfate-insoluble alpha-synuclein aggregation seen by Western blot analysis. In addition, there was a significant increase in oxidative stress, evidenced by elevated total protein carbonyl content, in cells treated with Mn-EBDC. Manipulation of intracellular reduced glutathione levels with N-acetyl-L-cysteine or L-buthionine sulfoximine pretreatment to modulate Mn-EBDC-mediated oxidative stress altered Mn-EBDC-mediated neurotoxicity, proteasomal dysfunction, and alpha-synuclein aggregation in these cells. These data suggest that neurotoxicity-induced by Mn-EBDC is at least partially attributable to Mn-EBDC-mediated proteasomal inhibition, and that the proteasome may be an important target by which environmental exposure modifies the risk for developing PD in vulnerable populations.

Amino Acid Sequence↗
PubMed2004

Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study.

There is little evidence to date to indicate if mesoaccumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux) approach was used to measure basal extracellular concentrations and extraction fractions of dopamine in the nucleus accumbens (ACB) of rats that self-administered nicotine i.v. for 25 days, as well as in rats serving as yoked comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final self-administration session, there was a significant reduction in basal extracellular dopamine levels in the ACB of the self-administration group compared with the yoked saline group (1.35+/-0.15 nM versus 3.70+/-0.28 nM). The basal extracellular dopamine levels in the yoked nicotine group (1.46+/-0.20 nM) were not significantly different compared with the nicotine self-administration group. The in vivo extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly increased in the nicotine self-administration (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%). In addition, a marked reduction in the elevation of extracellular dopamine levels in the ACB occurred after a nicotine challenge as measured by conventional microdialysis in the self-administration (112% of basal) and yoked nicotine (121% of basal) groups as compared with a yoked saline (154% of basal) group. The reduced basal ACB dopamine levels in the nicotine groups during early abstinence appears to be due to increased clearance, suggesting increased dopamine uptake is occurring as a result of the chronic nicotine treatment. The reduced elevation of extracellular dopamine levels in the ACB upon nicotine challenge suggests a functional desensitization or downregulation phenomenon involving acetylcholine receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a neuroadaptive change that alters dopamine transmission in the ACB during abstinence from chronic i.v. nicotine exposure.

Adaptation, Physiological↗
PubMed2004

Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature.

The hallmark of endothelial activation, an early and critical step in many alloimmune and inflammatory responses, is the transcriptional induction and expression of endothelial adhesion molecules (eg, vascular cell adhesion molecule-1 [VCAM-1]). We assessed the feasibility of VCAM-1-targeted in vivo detection of endothelial activation using I-125-labeled-F(ab')2 fragments of E1/6, a monoclonal antibody against human but not murine VCAM-1. The Kd and Bmax, determined by saturation binding in tumor necrosis factor (TNF)-activated human endothelial cells (ECs), were 3.2 +/- 0.6 nmol/L and 5600 +/- 300 binding sites per EC, respectively. Biodistribution and in vivo binding characteristics of I-125-E1/6 F(ab')2 were assessed in a novel chimeric human/mouse model, in which human skin (as a source of human microvasculature) is grafted onto SCID/beige mice. I-125-E1/6 F(ab')2 localized to TNF-activated human skin grafts as detected by autoradiography and gamma well-counting. Relative uptakes (uptake in human skin graft/uptake in the surrounding mouse skin) were, respectively, 2.6 +/- 0.8 (n = 14) and 1.6 +/- 0.3 (n = 12) for E1/6 and MOPC-21, an isotype-matched control antibody (P < .01). The preferential uptake in human skin graft was not due to differences in tissue vascularity assessed by Tc-99m-labeled murine red blood cells. In conclusion, the chimeric human/mouse model is a novel experimental tool for in vivo evaluation of human endothelial cell-specific radiopharmaceuticals. Although I-125-E1/6 F(ab')2 localized to human skin grafts, the limited number of VCAM-1 molecules/endothelial cell adversely affects its suitability as a target for in vivo imaging of endothelial activation.

Animals↗
PubMed2004

The effect of enrofloxacin on cell proliferation and proteoglycans in horse tendon cells.

Fluoroquinolone antibiotics have been used widely in humans and domestic animals, including horses, because of their broad-spectrum bactericidal activity, and relative safety. The use of fluoroquinolones, however, is not without risk. Tendonitis and spontaneous tendon rupture have been reported in people during or following therapy with fluoroquinolones. We have studied the effects of enrofloxacin, a fluoroquinolone antibiotic used commonly in domestic animals, on tendon cell cultures established from equine superficial digital flexor tendons. Effects on cell proliferation and morphology were studied using cell counting and scanning electron microscopy. Monosaccharide content and composition was determined by gas chromatography-mass spectrometry analysis. Western and Northern blot analyses were utilized to evaluate the synthesis and expression of two proteoglycans, biglycan and decorin. Our data demonstrate that enrofloxacin inhibits cell proliferation, induces morphological changes, decreases total monosacharide content and alters small proteoglycan synthesis at the glycosylation level in equine tendon cell cultures. These effects are more pronounced in juvenile tendon cells than in adult equine tendon cells. We hypothesize that morphological changes and inhibition of cell proliferation are a result of impaired production of biglycan and decorin, proteoglycans involved in fibrillogenesis of collagen, the most important structural component of the tendon of enrofloxacin-treated tendon cells. Our findings suggest that fluoroquinolones should be used with caution in horses, especially in foals.

Animals↗
PubMed2004

Cytotoxic effects of environmentally relevant chlorophenols on L929 cells and their mechanisms.

The chlorophenol chemicals (CPs) are a major class of widely distributed and frequently occurring persistent environmental pollutants. Pentachlorophenol (PCP) has been proposed to be procarcinogen in rodents and in possibly human beings. Human beings also easily expose to other chlorophenol chemicals, including 4-chlorophenol (CP), 2,4-dichlorophenol (DCP), 2,3,4-trichlorophenol (TCP), prompting this investigation of their comparative cytotoxic effects and cell death mechanisms, assayed in fibroblast L929 cells. The effective concentration for half-maximal response (EC50 values at 24 h for CP, DCP, TCP, and PCP are 2.18, 0.83, 0.46, and 0.11 mmol/L respectively and the EC50 values at 48 h are 1.18, 0.13, 0.08, and 0.06 mmol/L respectively by using 3-(4,5-dimethylthiazd-2-yl)-2,5-diphenyltentrazolium bromide (MTT) reduction assay. A clear structure-activity relationship was observed between toxicity of CPs and their octanol-water partition coefficients. The further studies indicate that CP, DCP, and TCP induce apoptosis in L929 cells in a concentration or time-dependent manner, but PCP mediates cell death more characteristic of necrosis than apoptosis. These results not only demonstrate that L929 cell growth inhibition bioassay may be useful to provide the comparative evaluation of toxicity of CPs in vitro, but also implicate that CP, DCP, TCP, in comparison with PCP, can induce L929 cell death by apoptosis, resulting in lower procarcinogensis, which may help to elucidate the molecular basis for the adverse health effects associated with CPs exposure.

Animals↗
PubMed2004

Local perfusion of nicotine differentially modulates somatodendritic dopamine release in the rat ventral tegmental area after nicotine preexposure.

We examined the effects of nicotine perfusion into the ventral tegmental area (VTA) on extracellular dopamine (DA) levels in rats using in vivo microdialysis. Local perfusion with nicotine for 80 min (10-100 microM) modestly increased (approximately 105-131% of basal) the extracellular DA levels in the VTA of rats that had been pretreated with saline for 5 days. In animals that had been pretreated with nicotine for 5 days (0.3 mg/kg, s.c.), perfusion with nicotine for 80 min (10-100 microM) dose-dependently increased the extracellular DA levels in the VTA of rats and did so to a greater extent than in saline-pretreated animals (125-171% of basal). Co-perfusion through the dialysis probe with 100 microM mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR) antagonist, or 100 microM dihydro-beta-erythroidine, a high affinity and competitive nAChR antagonist, attenuated the enhancement of extracellular DA levels produced by 100 microM nicotine alone. These results suggest that local nicotine challenge potentiated the somatodendritic DA release after nicotine preexposure by stimulation of high-affinity nAChRs in the VTA.

Animals↗
PubMed2004

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer.

BACKGROUND: The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer. METHODS: A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography. RESULTS: Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (P < 0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (P < 0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues. CONCLUSION: The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.

Adult↗
PubMed2004

CAR/PXR provide directives for Cyp3a41 gene regulation differently from Cyp3a11.

This study reports that Cyp3a41 gene contains 13 exons and is localized on the chromosome 5. CYP3A41 is a female-specific isoform that is predominantly expressed in the liver. Estrogen signaling is not responsible for its female specificity. CYP3A41 expression in kidney and brain is observed only in 50% of mice examined. PXR mediates dexamethasone-dependent suppression of CYP3A41. In contrast to CYP3A11, CYP3A41 expression is not induced by pregnenolone-16alpha-carbonitrile (PCN) in wild-type mice, but is significantly suppressed by PCN in PXR(-/-) mice. Phenobarbital and TCPOBOP induce CYP3A11 expression only in the presence of CAR, but have no effect on CYP3A41 expression. Immunoblot and erythromycin demethylase activity analysis reveal robust CYP3A induction after PCN treatment, which is poorly correlated to CYP3A41. These findings suggest a differential role for CAR/PXR in regulating individual CYP3A isoforms by previously characterized CYP3A inducers.

Animals↗