Biomedical subjects

Li Xu

Publications and source records attributed to Li Xu.

At least 55 records · Page 3Linked to original sources

PubMed2006

[Prevalence of putative periodontal microorganisms in Chinese patients with aggressive periodontitis].

OBJECTIVE: To evaluate the prevalence of putative periodontal microorganism in Chinese patients with aggressive periodontitis (AgP). METHODS: A total of 72 subgingival plaque samples were collected from 55 AgP patients and 17 healthy subjects. Seven putative periodontal microorganisms including Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Treponema denticola (Td), Campylobacter rectus (Cr), Prevotella intermedia (Pi) and Prevotella nigrescens (Pn) were detected by using 16S rRNA based polymerase chain reaction (PCR). RESULTS: The prevalence of Aa in AgP patients was very low (1.8%), while Pg, Tf, Td and Cr were more frequently detected in AgP patients (prevalence: 81.8%, 83.6%, 80% and 81.8%) than in healthy controls (prevalence: 17.6%, 11.8%, 5.9%, 29.4%, P < 0.01). CONCLUSIONS: The prevalence of Pg, Tf, Td and Cr were very high in aggressive periodontitis patients, and the combination of these bacteria may play an important role in AgP.

Adolescent↗

PubMed2006

[Measurement of IL-12 and IL-18 in sera of patients with autoimmune thyroid disease].

AIM: To provide some evidence for the imbalance of Th1/Th2 cells in patients with autoimmune thyroid disease(AITD). METHODS: Concentrations of IL-12 and IL-18 in the serum samples of 27 patients with Graves' disease(GD), 24 patients with euthyroid Hashimoto's thyroiditis(HT), 25 patients with hypothyroid HT and 20 normal controls were investigated by ELISA. The activity of thyroid-stimulating antibody(TSAb) was also assayed in GD patients. RESULTS: The mean levels of IL-12 and IL-18 in patients with GD and euthyroid HT were significantly higher than those in normal controls. Significant positive correlations were found between the level of IL-12 and IL-18 in the two groups. In addition, striking positive correlations were noted between the levels of IL-12, IL-18 and the activity of TSAb in GD, as well as between the levels of IL-12, IL-18 and the titers of anti-thyroglobulin antibody(TgAb) in euthyroid HT. However, no differences were observed in IL-12 and IL-18 levels between hypothyroid HT and normal controls. CONCLUSION: Th1-type cell and related cytokines might play an important role in the pathogenesis of HT and GD. Such therapies can aggravate the process of disease in GD by suppressing Th2 response and modulating imbalance toward Th1 predominance.

Adult↗

PubMed2006

[A novel method for detection and sero-grouping of Nesseria meningitidis].

OBJECTIVE: We developed a multiplex polymerase chain reaction (PCR) method for detection, identification and sero-grouping strains of N. meningitidis. METHODS: The gene of crgA was selected for detection and identification of N. meningitidis and the 230 bp of crgA fragments were amplified. The genes of siaD and orf-2 were used for sero-grouping. With this technology, N. meningitidis of serogroup A,B,C,Y and W135 can be differentiated from the specific fragment 400 bp,450 bp,250 bp, 120 bp,120 bp. RESULTS: This multiple PCR method seemed to be more sensitive than latex agglutination. We used this method to detect 61 isolates of N. meningitidis and the 230 bp of crgA fragments were amplified. No positive results were obtained from on 4 strains of non-N. meningitidis. It seemed that the PCR method which was based on crag, was specific in detecting N. meningitidis. The 55 strains of N. meningitidis could be grouped into A,B,C,Y and W135 by this multiplex PCR. No gene fragment was synthesized for the other serogroups of N. meningitidis. No cross-reaction was observed for other bacterial species. 4 samples of meningococcal meningitis patients were detected by the multiplex PCR and two of them were positive with 400 bp band,representing serogroup A of N. meningitidis but all were negative to culture and latex agglutination. 18 samples of Japanese (B) encephalitis patients were also detected by multiplex PCR and no positive result was obtained which was consistent to the finding from culture and latex agglutination. CONCLUSION: This multiplex PCR method showed its potential in clinical diagnosis and epidemiological investigation.

Bacterial Proteins↗

PubMed2006

[Blood lipids and glucose levels in patients with periodontitis].

OBJECTIVE: To determine the serum levels of lipid and glucose in patients with periodontitis. METHODS: The patients with aggressive periodontitis (AgP, n = 117) and chronic periodontitis (CP, n = 40) and healthy controls (n = 37) were recruited. Peripheral blood sample was obtained from each subject by venipuncture. Serum chemistry variables including total cholesterol, triglycerides, and fasting glucose were analyzed by biochemical analyzer. RESULTS: The average serum levels of triglycerides and glucose of the patients with AgP [(1.09 +/- 0.79) mmol/L and (5.07 +/- 0.66) mmol/L] were both significantly higher than those of the control group [(0.94 +/- 0.28) mmol/L and (4.62 +/- 0.64) mmol/L], P < 0.05. Higher serum levels of total cholesterol and glucose were also observed in patients with CP [(4.61 +/- 1.23) mmol/L and (5.40 +/- 1.01) mmol/L] compared with controls [(4.49 +/- 0.78) mmol/L and (4.62 +/- 0.64) mmol/L], P < 0.05. Serum level of total cholesterol in AgP group was positively associated with percentage of severe sites (r = 0.25, P < 0.01). CONCLUSIONS: Patients with periodontitis may have altered serum lipid and glucose levels compared with controls.

Adolescent↗

PubMed2006

[Influence of neoadjuvant chemotherapy on microsatellite instability in gastric carcinoma].

BACKGROUND & OBJECTIVE: Most results from clinical trials of neoadjuvant chemotherapy for gastric carcinoma are certain. Meanwhile, microsatellite instability (MSI) is thought to be a new mechanism of cell canceration. This study was to investigate the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. METHODS: Two microsatellite loci D2S123 and D3S1298 in tumor samples from 48 patients with gastric carcinoma, received preoperative chemotherapy of 5-fluorouracil (5-FU) and leucovorin (CF), were analyzed by polymerase chain reaction (PCR), electrophoresis on 8% denatured polyacrylamide gel, and silver staining. The microsatellite statuses of preoperative and postoperative specimens were compared. Chi-square test was used to analyze the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. RESULTS: The detection rate of MSI was significantly higher in preoperative samples than in postoperative samples (31.3% vs. 12.5%, P=0.026). After neoadjuvant chemotherapy, 9 cases changed from MSI-positive to MSI-negative, while no MSI-negative cases became MSI-positive. CONCLUSION: The neoadjuvant chemotherapy regimen of 5-FU/CF can induce some MSI-positive gastric carcinoma change to MSI-negative, but has no effect on MSI-negative cases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Establishment of model with inner ear mimetic aging and mtDNA 4834 bp deletion in rats].

OBJECTIVE: To explore the establishment of the mimetic aging effect in the inner ear of the rat. METHOD: Twenty-four Wistar rats were randomly divided into two groups: group A (D-galactose group, n = 14), which were treated with hypodermic 5% D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks and then with intraperitoneal saline for 10 days, and group B (control group, n = 10), which were given saline only. Auditory brainstem response(ABR) was used to detect the hearing threshold of rats, and colorimetry was used to analyze the activity of the glutathione peroxidase (GSH-PX). The inner ear tissue was harvested and mitochondrial DNA was amplified to identify the 4 834 bp deletion mutation by nested primer polymerase chain reaction (nested PCR) technique. RESULT: The incidence of mitochondrial DNA 4 834 bp deletion of group A was 100% (28/28), while the deletion of group B was 0. The activity of the GSH-PX in group A (59.07 +/- 8.70 U) was lower than that in group B (142.10 +/- 7.02 U). The difference between group A and group B was significant (t-test, P < 0.01). Variation in ABR threshold of (5.36 +/- 3.08) dB peSPL was observed in group A, and (6.50 +/- 3.37) dB peSPL in group B. The difference in shift of ABR threshold between group A and group B was not significant (P > 0.05). CONCLUSION: The mimetic aging effect in the inner ear of the rat can be induced by D-galactose, and this rat model presents high incidence of mtDNA4834 deletion. But no hearing loss was found in this model.

Aging, Premature↗

PubMed2005

Using comprehensive two-dimensional gas chromatography retention indices to estimate environmental partitioning properties for a complete set of diesel fuel hydrocarbons.

Comprehensive two-dimensional gas chromatography (GCxGC) provides nearly complete composition data for some complex mixtures such as petroleum hydrocarbons. However, the potential wealth of physical property information contained in the corresponding two-dimensional chromatograms is largely untapped. We developed a simple but robust method to estimate GCxGC retention indices for diesel-range hydrocarbons. By exploiting n-alkanes as reference solutes in both dimensions, calculated retention indices were insensitive to uncertainty in the enthalpy of gas-stationary-phase transfer for a suite of representative diesel components. We used the resulting two-dimensional retention indices to estimate the liquid vapor pressures, aqueous solubilities, air-water partition coefficients, octanol-water partition coefficients, and vaporization enthalpies of a nearly complete set of diesel fuel hydrocarbons. Partitioning properties were typically estimated within a factor of 2; this is not as accurate as some previous estimation or measurement methods. However, these relationships may allow powerful and incisive analysis of phase-transfer processes affecting petroleum hydrocarbon mixtures in the environment. For example, GCxGC retention data might be used to quantitatively deconvolve the effects of water washing and evaporation on environmentally released diesel fuels.

Journal Article↗

PubMed2005

Abundance, composition, and vertical transport of PAHs in marsh sediments.

Petroleum-derived hydrocarbons continue to persist in Wild Harbor, West Falmouth, MA, following a spill of No. 2 fuel oil in 1969 from the barge Florida. Recent analysis of marsh sediments revealed that residues of degraded oil are present with concentrations of total petroleum hydrocarbons as high as approximately 9 mg g(-1). Polycyclic aromatic hydrocarbons (PAHs) constitute only a minor fraction of these residues with maximum concentrations of 134 mirog g(-1), but their fate is of interest because of their potential toxicity to organisms. As compared to typical unweathered No. 2 fuel oil, the current distribution of PAHs in the sediments reflects substantial weathering by abiotic and biotic processes, specifically a preferential loss of naphthalenes relative to phenanthrenes, as well as isomer-specific biodegradation of alkylated PAHs. Based on comparison to results from an earlier study, it appears that little or no change has occurred to the distribution of PAHs since 1989, indicating that weathering at this site has stalled or is now proceeding at a significantly slower rate. To assess whether sediment-water partitioning and molecular diffusion in the interstitial medium are now the dominant processes controlling the vertical distribution of PAHs, downcore profiles were compared to a numerical model. While in some cases the model accurately reproduced the measured data, there were instances where the distribution of PAHs was slightly under or overestimated. Reasons for these discrepancies are discussed and are likely due to bioturbation, colloid-facilitated transport, or both. Assessment of the influence of these processes on the spilled oil expands our understanding of the overall fate of these compounds and their potential long-term effects on the environment.

Geologic Sediments↗

PubMed2005

Mood stabilizing drug lithium increases expression of endoplasmic reticulum stress proteins in primary cultured rat cerebral cortical cells.

The mood stabilizing drug lithium is a highly effective treatment for bipolar disorder. Previous studies in our laboratory found that chronic treatment with the mood stabilizing drug valproate in rat brain increased the expression of endoplasmic reticulum (ER) stress proteins GRP78, GRP94 and calreticulin. We report here that in primary cultured rat cerebral cortical cells, expression of GRP78, GRP94 and calreticulin are increased not only by valproate, but also by lithium after chronic treatment for 1 week at therapeutically relevant concentrations. However, two other mood stabilizing drugs carbamazepine and lamotrigine had no effect on expression of GRP78, GRP94 or calreticulin. Chronic treatment with lithium for 1 week increased both mRNA and protein levels of ER stress proteins. In contrast to a classic GRP78 inducer thapsigargin, an inhibitor of the ER Ca2+ -ATPase, chronic treatment with lithium or valproate for 1 week modestly increased GRP78 expression in neuronal cells, had no effect on basal intracellular free Ca2+ concentration and does not induce cell death. These results indicate that lithium and valproate may increase expression of GRP78, GRP94 and calreticulin in primary cultured rat cerebral cortical cells without causing cell damage. These results also suggest that the mechanism of GRP78 increase induced by lithium and valproate may be different from that of thapsigargin.

Animals↗

PubMed2005

A novel thiol oxidation-based mechanism for adriamycin-induced cell injury in human macrophages.

Adriamycin is a widely used antitumor antibiotic, but its use has been limited by its cytotoxicity in both cardiomyocytes and non-cardiac tissues. While adriamycin's ability to redox cycle via one-electron transfer reactions and generate ROS is thought to promote cardiotoxicity, the mechanisms involved in non-cardiac tissue injury are not clear. Here we show that prolonged exposure (48 h) of human monocyte-derived macrophages to adriamycin at concentrations as low as 1 microM promotes caspase-independent cell death. Treatment of cells with scavengers of superoxide and peroxyl radicals blocked adriamycin-induced oxidation of dichlorodihydrofluorescein (DCFH) but did not prevent macrophage injury. Macrophages treated with either adriamycin or the thiol oxidant diamide showed elevated levels of glutathione disulfide and increased protein-S-glutathionylation prior to cell injury, indicating that thiol oxidation is involved in adriamycin-induced macrophage death. Furthermore, inhibition of glutathione reductase (GR) with 1,3-bis[2-chloroethyl]-1-nitrosourea or transfection of macrophages with small inhibitory RNA (siRNA) directed against GR or glutaredoxin (Grx) potentiated adriamycin-induced macrophage injury. Thus, both GR and Grx appear to play a crucial role in protecting macrophages from adriamycin-induced cell injury. These findings suggest a new mechanism for adriamycin-induced tissue injury whereby thiol oxidation, rather than one-electron redox cycling and ROS generation, mediates adriamycin-induced cell damage.

Antineoplastic Agents, Alkylating↗

PubMed2005

[Long-term results of surgical treatment of stomach cancer: clinical experience of forty years from Sun Yat-sen University Cancer Center].

OBJECTIVE: To investigate the approaches to improve therapeutic effect of stomach cancer by analysis of the long-term results of surgical treatment of this disease. METHODS: Prognostic factors of stomach cancer were analyzed by Cox multivariate regression model based on clinical data of 2561 stomach cancer cases who underwent surgical treatment from 1964 to 2004 at Sun Yat-sen University Cancer Center. Survival rates were calculated by life table method. RESULTS: Gastrectomy was performed for 1950 cases with resectability of 76.1%, among which there were 1192 cases of curative resection (46.5%) and 758 cases of non-curative resection (29.6%). The other 611 cases of palliative operation included bypass procedures and laparotomy. Operative mortality of all cases was 0.8% and morbidity was 5.1%. For all cases the 1-, 3- and 5-year survival rate was 52.4%, 38.6% and 35.5%, respectively. The stage-specific 5-year survival rate was 86.8% (Stage I), 58.7% (Stage II), 28.4% (Stage III) and 7.6% (Stage IV), respectively. The 5-year survival after curative resection in the period of 40 years was 45.5%, and increased to 52.7% in the last two decades and 61.8% in recent decade. Stage-specific case proportion during the earlier two decades was 1.4% (Stage I), 10.6% (Stage II), 23.1% (Stage III) and 64.9% (Stage IV), respectively, and that during the recent two decades was 9.3%, 18.5%, 35.3% and 36.8%, respectively. The 5-year survival rate of cases during the earlier two decades was 18.0% and increased to 37.5% during the recent two decades. Multivariate analysis indicated that main prognostic factors of stomach cancer included TNM staging, curative resection and multidisciplinary treatment. CONCLUSIONS: Early detection and curative resection were the most important measures to improve therapeutic effect of stomach cancer. A surgery-predominant multidisciplinary treatment individualizing biological characteristics of tumor, staging of disease and tumor site will contribute to improvement of therapeutic effect of stomach cancer.

Adolescent↗

PubMed2005

In situ measurement of neuronal nitric oxide synthase activity in the spinal cord by NADPH-diaphorase histochemistry.

NADPH-diaphorase (NADPH-d) histochemistry has provided a simple method to stain neuronal nitric oxide synthase (nNOS)-containing neurons in the central nervous system. In the spinal cord, NO formation following activation of N-methyl-D-asparate (NMDA) receptors plays a crucial role in nociceptive processing. To investigate the molecular mechanisms, we attempted to evaluate nNOS activity in situ using isolated intact spinal cord preparation and NADPH-d histochemistry. NADPH-d activity in the superficial layer of the spinal cord increased gradually with ages from P10 to P30 and NMDA enhanced the NADPH-d staining in a time- and concentration-dependent manner. The NMDA-stimulated NADPH-d staining was inhibited by NMDA receptor antagonists, but not by non-NMDA and metabotropic glutamate receptor antagonists. The NADPH-d staining showed a pronounced stereospecificity for beta-NADPH and completely suppressed by dichlorophenolindophenol, an artificial electron acceptor. NMDA-evoked NO formation in the spinal cord was confirmed by the fluorescent NO indicator diaminofluorescein-FM (DAF-FM). These results demonstrate that NADPH-d activity in the superficial spinal cord is ascribed to nNOS activity and is dependent on NMDA. A combination of isolated intact spinal cord preparations and NADPH-d histochemistry may provide a unique system to elucidate biochemical and molecular mechanisms for nNOS activation in the spinal cord.

Animals↗

PubMed2005

Psychophysical metrics and speech recognition in cochlear implant users.

Intersubject variability in perception is a prominent characteristic of people with cochlear implants. This study characterized intersubject differences using simple metrics based on psychophysical measures: maximum comfortable loudness levels (C levels) and dynamic ranges (DRs). In a group of 17 subjects, we assessed across-site variation (ASV) and across-site mean (ASM) values of C levels and DRs for bipolar (BP) and monopolar (MP) stimulation, and examined the relation of these metrics to speech recognition across subjects. Significant negative correlations with speech recognition were found for ASVs of C levels for BP stimulation; i.e., subjects with high ASVs of BP C levels had poor speech recognition. Positive correlations with speech recognition were found for ASMs of C levels and ASMs of DRs for both BP and MP stimulation; i.e., subjects with high mean C levels and large mean DRs had better speech recognition. Thus, these psychophysical metrics are effective for diagnosis of individual differences in performance of subjects with cochlear implants. Furthermore, they point to some potentially useful treatment procedures.

Adult↗

PubMed2005

Direct detection and quantification of Alternaria alternata lycopersici toxins using high-performance liquid chromatography-evaporative light-scattering detection.

Alternaria alternata lycopersici toxins are produced by the tomato pathogenic fungus A. alternata f. sp. lycopersici. They are primary determinants for stem canker disease of tomato and induce apoptosis in animals and plants. Due to the lack of a UV chromophore, their detection has relied on derivatizations or immunoassays, which require tedious pre-assay processes. Here, we describe a method for direct and quantitative detection of the toxins. The method employs an evaporative light-scattering detector (ELSD) coupled to HPLC. It gives a linear response in the range of 400-4000 ng toxin, with a detection limit of about 6 ng/mul. The detection of all major toxin congeners by HPLC-ESLD was confirmed by liquid chromatography-mass spectrometry. Thus, the method provides a simple and sensitive tool for the studies of this group of host-specific mycotoxins.

Alternaria↗

PubMed2005

Mouse estrogen receptor beta isoforms exhibit differences in ligand selectivity and coactivator recruitment.

Estrogens exert their physiological effects through two estrogen receptor (ER) subtypes, ERalpha and ERbeta. In mouse, the cloning of an alternative splice variant of the wild-type ERbeta (mERbeta1), mERbeta2, which contains an 18 amino acid insertion in the ligand binding domain, contributed an additional level of complexity to estrogen signaling. In this study we have assayed the interaction of several known ligands with mERbeta1 and mERbeta2. The binding affinity of estradiol was 14-fold higher for mERbeta1 than for mERbeta2. In contrast, raloxifene was dramatically (8-fold) mERbeta2 selective. The selectivity for mERbeta2 was abolished when the 2-arylbenzothiophene core of the raloxifene molecule was tested for binding affinity, demonstrating that the 3-aroyl side chain of raloxifene plays an important role in contributing to its mERbeta2 selectivity. The opposite isoform selectivity found for estradiol and raloxifene in our ligand binding assay was also reflected in the transactivation assay system. That is, mERbeta2 required 10-fold greater estradiol concentrations for maximal activation compared to mERbeta1, whereas raloxifene was more potent in antagonizing estradiol-induced gene expression via mERbeta2 than mERbeta1. The raloxifene core behaved as a pure agonist. Furthermore, mERbeta2 showed significantly decreased estradiol-induced maximal transcriptional activity as compared to mERbeta1. A pull-down assay indicated that the interactions of TIF2 and RAP250 with mERbeta2 were weaker than with mERbeta1. To assess TIF2 and RAP250 interactions with ERs more quantitatively, we examined the interaction of LXXLL containing peptides derived from TIF2 and RAP250 with mERbeta1 and mERbeta2 using surface plasmon resonance analysis. Our results indicate that mERbeta2 interacts with both coactivators with lower affinity, which may explain its reduced transcriptional activity. Taken together, these results suggest that ligand selectivity and coactivator recruitment of the ERbeta isoforms constitute additional levels of specificity that influence the transcriptional response in estrogen target cells.

Animals↗

PubMed2005

A series of single, double, and triple Me2biim-bridged dinuclear, trinuclear, and polymeric complexes: syntheses, crystal structures, and luminescent properties.

Reaction of ZnCl(2) and Me(2)biim (Me(2)biim = N,N'-dimethyl-2,2-'-biimidazole) in acidic or neutral aqueous solutions gave the noncoordinated ZnCl(4).H(2)Me(2)biim (1) or the double Me(2)biim bridged [Zn(2)Cl(4)(mu-Me(2)biim)(2)] (2). Use of CdX(2) (X = Cl, Br, I) instead of ZnCl(2) yielded the single Me(2)biim bridged one-dimensional coordination polymer [CdX(2)(mu-Me(2)biim)](n) (X = Cl, 3; Br, 4; I, 5). The stacking of the infinite chains are dominated by C-H...X interactions in 3 and 4 but by I...I interactions in 5, responsible for their different crystal structures. Use of Zn(NO(3))(2) instead of ZnCl(2) produced the novel triple Me(2)biim-bridged [Zn(2)(mu-Me(2)biim)(3)(H(2)O)(2)](NO(3))(4).H(2)O (6). The unprecedented hexa-Me(2)bim bridged trinuclear [Cd(3)(mu-Me(2)biim)(8)](2)(ClO(4))(12)(H(2)O)(6) (7) was obtained by using Cd(CH(3)CO(2))(2) in the presence of NaClO(4). Compounds 1-7 were characterized by X-ray crystallography and IR. Examination of photophysical properties of 1-7 indicates that the fluorescence emission of Me(2)biim has been effectively enhanced, quenched, or shifted in its metal complexes 1-7.

Journal Article↗

PubMed2005

Contribution of biomass burning to atmospheric polycyclic aromatic hydrocarbons at three European background sites.

Radiocarbon analysis of atmospheric polycyclic aromatic hydrocarbons (PAHs) from three background areas in Sweden, Croatia, and Greece was performed to apportion their origin between fossil and biomass combustion. Diagnostic ratios of PAHs implied that wood and coal combustion was relatively more important in the northern European site, while combustion of fossil fuels was the dominant source of PAHs to the two central-southern European background sites. The radiocarbon content (delta14C) of atmospheric PAHs in Sweden ranged between -388 per thousand and -381 per thousand, while more depleted values were observed for Greece (-914 per thousand) and Croatia (-888 per thousand). Using a 14C isotopic mass balance model it was calculated that biomass burning contributes nearly 10% of the total PAH burden in the studied southern European atmosphere with fossil fuel combustion making up the 90% balance. In contrast, biomass burning contributes about 50% of total PAHs in the atmosphere at the Swedish site. Our results suggest that the relative contributions of biomass burning and fossil fuels to atmospheric PAHs may differ considerably between countries, and therefore, different national control strategies might be needed if a further reduction of these pollutants is to be achieved on a continental-global scale.

Air Pollutants↗

PubMed2005

Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells.

Epidemiologic studies associate consumption of genistein, in the form of dietary soy, with lower rates of metastatic prostate cancer. We have previously shown that genistein inhibits prostate cancer cell detachment in vitro, that it is well tolerated in an older cohort of men with prostate cancer, and that it alters cell signaling in that same cohort. We have also shown that p38 mitogen-activated protein kinase (MAPK) is necessary for transforming growth factor beta (TGF-beta)-mediated increases in prostate cancer adhesion. Although cell invasion is closely linked to metastatic behavior, little is known about how this process is regulated in prostate cancer or what effect, if any, genistein has on associated processes. We now show that genistein inhibits matrix metalloproteinase type 2 (MMP-2) activity in six of seven prostate cell lines tested, blocks MMP-2 induction by TGF-beta, and inhibits cell invasion. Efficacy was seen at low nanomolar concentrations, corresponding to blood concentrations of free genistein attained after dietary consumption. Inhibition of p38 MAPK by either SB203580 or dominant-negative construct blocked induction of MMP-2 and cell invasion by TGF-beta. Genistein exerted similar effects and was found to block activation of p38 MAPK by TGF-beta. This study shows that p38 MAPK is necessary for TGF-beta-mediated induction of MMP-2 and cell invasion in prostate cancer and that genistein blocks activation of p38 MAPK, thereby inhibiting processes closely linked to metastasis, and does so at concentrations associated with dietary consumption. Any potential causal link to epidemiologic findings will require further investigation.

Cell Line↗