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Biomedical subjects

L Zhu

Publications and source records attributed to L Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Aberrant methylation of cyclooxygenase-2 in breast cancer patients.

BACKGROUND: Although aberrant CpG island methylation and subsequent silencing of the cyclooxygenase-2 (COX-2) promoter has been observed in colorectal and gastric tumors recently, little is known about that in breast cancers. The aim of this study was to identify the methylation status of COX-2 as well as to determine the association between clinical characteristics and COX-2 methylation in breast cancer patients. METHODS: Using bisulfite modification and a methylation-specific PCR, we examined the methylation status of the COX-2 promoter in primary tumors from 110 breast cancer patients. Meanwhile, the expression of COX-2 protein was determined by immunohistochemistry (IHC). RESULTS: Twenty out of 110 (18.2%) primary breast cancers showed aberrant methylation of the 5' region of COX-2. Loss of expression of COX-2 protein was found in all tumors with COX-2 methylation. Methylation of COX-2 was strongly correlated with tumor size (P = 0.026), presence of axillary lymph node metastasis (P = 0.001) and lymphovascular permeation (P = 0.034). CONCLUSION: Our data suggest that COX-2 methylation is associated with good prognostic factors in breast cancer patients. COX-2 promoter methylation may be one of the mechanisms by which tumor cells regulate COX-2 expression.

Adult↗
PubMed2005

Cyclooxygenase-2 expression is associated with VEGF-C and lymph node metastases in gastric cancer patients.

Previous studies have suggested that cyclooxygenase-2 (COX-2) over-expression is associated with angiogenesis in gastric cancer. However, the relationship between COX-2 and lymphangiogenesis is still unclear. The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenic factor, vascular endothelial growth factor-C (VEGF-C), in human gastric cancer, as well as to correlate with clinicopathological parameters. Sixty-three gastric cancer patients underwent radical gastrectomy (D2 or D3) were enrolled in this study. The expression of COX-2 and VEGF-C were detected by immunohistochemistry, and the small lymphatic vessels were immunohistochemically stained by LYVE-1 antibody. The association between COX-2 and VEGF-C expressions and clinicopathological parameters (such as gender, tumor location, lymph node status and Lauren classification) were determined. VEGF-C over-expression was observed in 33 of 63 patients (52%), while COX-2 over-expression occurred in 42 of 63 tumor samples (67%). Presence of microlymphatic vessels with LYVE-1 staining was found in 35 cases. COX-2 over-expression was highly correlated with VEGF-C over-expression (P = 0.032), microlymphatic vessels (P = 0.002) as well as presence of metastatic lymph nodes (P = 0.007). However, no significant correlation was found between COX-2 expression and other clinicopathological parameters. Our data suggest that COX-2 expression is associated with lymphangiogenesis and lymph node metastasis in human gastric carcinoma. This raises the possibility that COX-2-mediated VEGF-C over-expression might promote lymph node metastasis via lymphangiogenesis pathway in patients with gastric cancer.

Aged↗
PubMed2005

Study of COX-2, Ki67, and p53 expression to predict effectiveness of 5-flurouracil, epirubicin and cyclophosphamide with celecoxib treatment in breast cancer patients.

BACKGROUND: Cyclooxygenase-2 (COX-2) affects cell proliferation, apoptosis, and metastasis of breast cancer, and may also be involved in tumor angiogenesis through vascular endothelial growth factor. Ki67 and p53 are common markers of proliferation and apoptosis in tumor cells. This study investigated the change in expression of COX-2, Ki67, and p53 in solid tumors after the administration of chemotherapeutic drugs. MATERIALS AND METHODS: Fifty patients were eligible to be treated with preoperative 5-fluorouracil, epirubicin, and cyclophosphamide, with celecoxib (FECC). Tumor tissue samples from 10 patients who, diagnosed with invasive ductal carcinoma, completed chemotherapy were examined immunohistochemically for COX-2, Ki67, and p53. RESULTS: From the 60% of patients who expressed COX-2 and 90% who expressed Ki67 and p53 before treatment, 90% of patients revealed a lower intensity staining for each marker after FECC treatment. However, changes in expression of the three markers did not significantly correlate with tumor size, grade, axillary lymph node status. Immunostained slides clearly showed that the diaminobenzidine intensity was markedly reduced after the three-cycle FECC treatment, which implied the combined regimens be effective to the cancer patients. CONCLUSIONS: This study demonstrates a novel relationship between COX-2, Ki67, and p53 expression of human breast invasive ductal carcinomas. This functional relationship provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer.

Adult↗
PubMed2005

Circulating tumor cells in patients with breast cancer: possible predictor of micro-metastasis in bone marrow but not in sentinel lymph nodes.

BACKGROUND: Blood and lymphatic circulation are the major routes during metastatic spread of breast cancer cells. Despite the predictive and prognostic value of bone marrow (BM) micro-metastasis, repeated and frequent BM aspirations may not be easily accepted by patients. We try to establish the role of circulating tumor cells as a predictor for micro-metastasis in BM and sentinel lymph node (SLN) as well as to identify the association between micro-metastasis in blood and lymphatic circulation. We prospectively studied 47 breast cancer patients without overt metastasis. Bilateral BM samples and blood samples were obtained before surgery and subsequently handled using magnetic-activated cell separation (MACS) followed by immunocytochemistry (ICC). SLN was examined by hematoxylin and eosin (H and E) staining and ICC. RESULTS: Blood and BM micro-metastasis were detected in 16 (35%) and 25 (54%) of 47 patients. SLN micro-metastasis were detected in 13 (27.7%) and 22 (46.8%) patients using H and E and ICC, respectively. All the patients with circulating tumor cells had micro-metastasis in BM, whereas 9 of 25 (36%) patients with micro-metastasis in BM had no circulating tumor cells (P < 0.001). On the other hand, there is no correlation between circulating tumor cells and micro-metastasis in SLNs detected by either H and E (P = 0.52) or ICC (P = 0.36). We found that the presence of circulating tumor cells might predict BM micro-metastasis but not SLN micro-metastasis. It is also interesting to find that the presence of SLN micro-metastasis does not necessarily correlate with the presence of micro-metastasis in BM and blood.

Adult↗
PubMed2005

DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma.

BACKGROUND: Neoplastic cells often display aberrant methylation and silencing of multiple genes, including tumor suppressor genes (TSGs) that regulate critical processes such as cell cycle control, DNA repair and angiogenesis. Tissue inhibitor of metalloproteinase-3 (TIMP3) is an extracellular matrix-bound protein which regulates matrix composition and affects tumor growth, invasion and angiogenesis. It mediates vascular endothelial growth factor (VEGF) by blocking the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling. This study focused on the hypermethylation status of the TIMP3 gene with clinical parameters in invasive breast ductal carcinoma (IDC) samples. MATERIALS AND METHODS: DNA extraction and methylation specific PCR (MSP) was performed on 173 patients with invasive breast carcinoma. Both specific methylated and unmethylated primers for each gene were used for PCR and the products were visualized on agarose gel. The methylation status of TIMP3 was then compared with corresponding patients' clinicopathologic characteristics. RESULTS: Methylation frequencies of TIMP3 in the breast cancer samples were 20.81 %. Among the hypermethylated cancers, 50% were tumor grade II-III, 44.44% were positive in lymph node involvement (LN), 36.11% were positive in lymphovascular permeation (LVP); 44.44%, 22.22% and 47.22% for the overexpressions in estrogen receptor (ER), progesterone receptor(PR) and c-erbB2, respectively. CONCLUSION: The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis, and overexpression of ER, PR and c-erbB2, respectively.

Breast Neoplasms↗
PubMed2005

The value of bone marrow aspirates culture for the detection of bone marrow micrometastasis in breast cancer.

BACKGROUND: Detection of micrometastasis is an important problem of clinical significance for a better understanding and control of tumor progression, which will improve patients' survival time. Tumor cells in bone marrow (BM) aspirates are indicative of the general disseminative metastasis in patients with early breast cancer and characterization of breast cancers by various tumor markers which are appropriate for the identification of high risk groups. MATERIALS AND METHODS: Bone marrow aspirates were obtained from 44 breast cancer patients at the time of surgery. To identify micrometastases in bone marrow, an immunocytochemical assay for epithelial cytokeratin (CK) was performed at the second passage after selective culture. Cytokeratin-positive bone marrow disseminated cancer cells were observed in more than 90% of the patients. This high incidence needs further investigation with bigger sample size to confirm. However, these results indicate that this technique can be used as an early diagnostic technique of bone marrow micrometastases in the patient with breast cancer thereby promoting the development of therapeutic strategy. High incidences need further investigation with bigger samples to confirm.

Biopsy, Needle↗
PubMed2005

Upregulation of T-bet expression in peripheral blood mononuclear cells during Vogt-Koyanagi-Harada disease.

AIM: To test the hypothesis that T-bet expression is altered in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: Peripheral blood was withdrawn from 16 VKH patients before and after immunosuppressive treatment and from 16 healthy individuals. IFN-gamma, IL-2, and IL-4 in the serum and the supernatants of peripheral blood mononuclear cells (PBMC) cultured with or without phytohaemagglutinin (PHA) were measured by ELISA. T-bet mRNA and protein expression in PBMC cultured with or without PHA was detected by RT-PCR and western blot, respectively. RESULTS: The level of IFN-gamma, but not IL-2 and IL-4, was significantly higher in the supernatants of stimulated PBMC in patients than in controls. A significantly increased T-bet mRNA was found in VKH patients during an active uveitis episode, but not in quiescent patients, compared to controls. T-bet protein was detectable in VKH patients during an active uveitis episode, but not in quiescent patients nor in the healthy controls. Stimulation of PBMC with PHA resulted in a marked upregulation of T-bet mRNA and protein expression for both patients and controls with no significant difference between the two groups. CONCLUSIONS: Upregulation of T-bet may be associated with the development of a Th1 mediated immune response in VKH disease.

Adult↗
PubMed2004

In situ vesicle-template-interface reaction to self-encapsulated microsphere CdS.

An in situ vesicle-template-interface reaction route was introduced to prepare self-encapsulated CdS microspheres, which can be obtained by heating an ethanol solution after ultrasonic irradiation in the presence of Cd(NO3)2, CS2, and sodium dodecyl sulfate. The products were characterized by various techniques of XRD, TEM, UV-Vis spectrum, and PL spectrum.

Journal Article↗
PubMed2004

Cardioprotective effects of desflurane: effect of timing and duration of administration in rat myocardium.

BACKGROUND: We compared the cardioprotective effects of 1 minimum alveolar concentration (MAC) desflurane administered before, during or after ischaemia, or throughout the experiment (before, during and after ischaemia) on myocardial infarct size following 30 min occlusion of the left anterior descending coronary artery and 3 h reperfusion in adult rats. METHODS: Fifty male Sprague-Dawley rats were anaesthetized with pentobarbital, intubated and mechanically ventilated. Blood gases, pH and body temperature (37.5-38 degrees C) were controlled. Heart rate and arterial pressure were measured continuously. Animals were randomly assigned to the following groups (n=10 in each group): pentobarbital only ("Pento"); 15 min desflurane administration followed by 10 min of washout before 30 min ischaemia and 3 h reperfusion ("Precond"); 30 min desflurane administration during ischaemia period ('Isch'); desflurane administration during the 15 first min of reperfusion ("Reperf") and desflurane administration throughout the experiment (before, during and after ischaemia; "Long"). Volumes at risk and infarct sizes were assessed by Indian ink and with 2,3,5-triphenyltetrazolium chloride staining, respectively. RESULTS: Physiological parameters and volumes at risk were not significantly different between groups. In the Pento group, mean myocardial infarct size was 65 (sd 15)% of the volume at risk; myocardial infarct size was reduced to a significant and comparable extent in the desflurane-treated groups (Precond 42 (14)%; Isch 34 (11)%; Reperf 41 (15)%; Long 33 (10)%; P<0.0002 vs Pento group). CONCLUSIONS: In rats, desflurane 1 MAC significantly decreased myocardial infarct size whatever the period and duration of administration.

Adjuvants, Anesthesia↗
PubMed2004

Precision measurement of the neutron spin asymmetryA(n)(1) and spin-flavor decomposition in the valence quark region.

We have measured the neutron spin asymmetry A(n)(1) with high precision at three kinematics in the deep inelastic region at x=0.33, 0.47, and 0.60, and Q(2)=2.7, 3.5, and 4.8 (GeV/c)(2), respectively. Our results unambiguously show, for the first time, that A(n)(1) crosses zero around x=0.47 and becomes significantly positive at x=0.60. Combined with the world proton data, polarized quark distributions were extracted. Our results, in general, agree with relativistic constituent quark models and with perturbative quantum chromodynamics (PQCD) analyses based on the earlier data. However they deviate from PQCD predictions based on hadron helicity conservation.

Journal Article↗
PubMed2004

Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis.

BACKGROUND: Prostate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF-I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF-I in conjunction with endogenous IGF-I contributes to the osteoblastic phenotype characteristic of metastatic PC. METHODS: To test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines. RESULTS: Using RIA, we found serum-free conditioned media (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real-time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2. C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/- 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2 and C4-2B and at least equivalent protein expression. CONCLUSIONS: Our results suggest that PC cells that have metastasized to bone have an upregulated IGF-I regulatory system. This suggests an activated IGF-I axis contributes to the host-PC interaction in promoting osteoblastic metastases.

Bone Neoplasms↗
PubMed2004

Interleukin-1beta and tumor necrosis factor-alpha produce distinct, time-dependent patterns of acute arthritis in the rat knee.

Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) synergistically induce and sustain arthritis. Two competing hypotheses of arthritis induction are 1) that TNF preferentially mediates inflammation, whereas IL-1 impels bone destruction, or 2) that either cytokine controls the entire process. In this study, these propositions were tested in two experiments by instilling IL-1beta or TNF-alpha into one knee of Lewis rats (n = 6/group) to incite arthritis, after which semiquantitative scores for inflammation, bone resorption, osteoclasts, and cartilage integrity were acquired. In the induction study, IL-1beta or TNF-alpha (3, 10, or 30 micro g) was given once to incite arthritis. After 2 days, IL-1beta induced significant, dose-dependent increases in inflammation (mild to marked), bone resorption (minimal to moderate), and osteoclasts (minimal to moderate). In contrast, TNF-alpha induced minimal to mild inflammation but had little impact on resorption or osteoclasts. Both IL-1 and TNF (>/=10 micro g) yielded mild cartilage degeneration. Most lesion scores in TNF-treated rats were significantly lower than those in animals given the same dose of IL-1beta. In the persistence study, rats were injected once with IL-1 or TNF (10 micro g) and maintained for 2, 3, or 7 days. IL-1beta significantly enhanced inflammation (all 3 days), bone resorption (days 2 and 3), osteoclasts (days 2 and 3), and cartilage matrix loss (days 2 and 3), whereas TNF-alpha augmented inflammation (days 2 and 3) and cartilage degeneration (day 2) but not bone resorption or osteoclasts. Thus, both IL-1beta and TNF-alpha can launch inflammation, but IL-1beta drives skeletal destruction.

Animals↗
PubMed2003

Divergence of the grüneisen ratio at quantum critical points in heavy fermion metals.

We present low-temperature volume thermal expansion, beta, and specific heat, C, measurements on high-quality single crystals of CeNi2Ge2 and YbRh2(Si0.95Ge0.05)(2) which are located very near to quantum critical points. For both systems, beta shows a more singular temperature dependence than C, and thus the Grüneisen ratio Gamma proportional to beta/C diverges as T-->0. For CeNi2Ge2, our results are in accordance with the spin-density wave (SDW) scenario for three-dimensional critical spin fluctuations. By contrast, the observed singularity in YbRh2(Si0.95Ge0.05)(2) cannot be explained by the itinerant SDW theory but is qualitatively consistent with a locally quantum critical picture.

Journal Article↗
PubMed2003

Estrogen levels and estrogen receptors in patients with stress urinary incontinence and pelvic organ prolapse.

OBJECTIVES: To investigate the histologic characteristics of tissues presumed to be the cause of urinary stress incontinence and pelvic organ prolapse. METHODS: Cardinal ligament and uterosacral ligament samples were obtained from 73 women undergoing hysterectomy. The evaluation of estrogen receptors (ERs) by immunohistochemical staining was semi-quantitative. Serum estrogen was determined by ELISA. Statistical analyses were performed by the independent-sample t-test and one-way ANOVA. RESULTS: Serum estradiol levels and ER values in the premenopausal women with pelvic organ prolapse were significantly lower than in the control group (P<0.01). A positive correlation was found between ERs and the number of postmenopausal years (P<0.01). ER values were similar in the cardinal and uterosacral ligaments. CONCLUSIONS: Serum estrogen levels and ER values are significantly lower in the uterine ligaments of premenopausal women with pelvic organ prolapse, and there was a positive correlation between ER values in the uterine ligaments and the duration of postmenopausal years. Serum estrogen levels and ER values were similar in the cardinal ligament and the uterosacral ligament.

Adult↗
PubMed2003

Genistein directly blocks glycine receptors of rat neurons freshly isolated from the ventral tegmental area.

The effects of tyrosine kinase inhibitors on the glycine-induced current (I(Gly)) were studied in rat neurons freshly isolated from the ventral tegmental area (VTA). Genistein reversibly and concentration-dependently depressed I(Gly), with an IC(50) of 13 microM. Preincubation with genistein had no effect on I(Gly), indicating that genistein is effective only when glycine is bound to the receptor and channels are most likely open. Genistein depressed maximum I(Gly) without significantly changing the EC(50) for glycine. Genistein-induced inhibition of I(Gly) was sensitive to membrane voltage, being greater at positive membrane potentials. A kinetic analysis indicated that genistein lengthens the time constant of I(Gly) activation, but has no effect on deactivation or desensitization. When genistein was rapidly washed out, a transient rebound current probably reflected a faster dissociation of genistein, with respect to glycine. Results of competition experiments suggest that genistein acts on the same region of the glycine receptor as picrotoxin. Daidzein, an analog of genistein that does not act on protein kinases, also inhibited I(Gly). Co-application of lavendustin A, a specific inhibitor of tyrosine kinase, had no effect on I(Gly). Our results extend to neurons isolated from the VTA, the previous finding that genistein directly inhibits glycine receptors of hypothalamic brain slices.

Animals↗
PubMed2003

Palmar plate fixation of AO type C2 fracture of distal radius using a locking compression plate--a biomechanical study in a cadaveric model.

The stability of palmar plate fixation using a locking compression T-plate was compared with that of a conventional palmar T-plate and a dorsal T-plate in a cadaveric model of an AO type C2 fracture of distal radius. The wrist axial load transmission through the radius was tested for each fixation. The results show that, under 100N axial load, the palmar locking compression T-plate restores stability comparable to that of the intact radius, and is superior to conventional palmar or dorsal T-plates.

Biomechanical Phenomena↗
PubMed2003

A change in the pattern of activity affects the developmental regression of the Purkinje cell polyinnervation by climbing fibers in the rat cerebellum.

Pattern of activity during development is important for the refinement of the final architecture of the brain. In the cerebellar cortex, the regression from multiple to single climbing fiber innervation of the Purkinje cell occurs during development between postnatal days (P) 5 and 15. However, the regression is hampered by altering in various ways the morpho-functional integrity of the parallel fiber input. In rats we disrupted the normal activity pattern of the climbing fiber, the terminal arbor of the inferior olive neurons, by administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87) after harmaline treatment multiple (double only) climbing fiber EPSC-steps persist in 28% of cells as compared with none in the control. The ratio between the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases in parallel with the decline of the polyinnervation factor, indicating a gradual enlargement of the synaptic contribution of the winning climbing fiber synapse at the expense of the losing one. Harmaline treatment had no later effects on the climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36). However, there was a rise in the paired-pulse depression indicating a potentiation of the presynaptic mechanisms. In the same period, after harmaline treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The distribution of parallel fiber synaptic boutons was also not changed. Thus, a change in the pattern of activity during a narrow developmental period may affect climbing fiber-Purkinje cell synapse competition resulting in occurrence of multiple innervation at least up to 3 months of age. Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development. They suggest that many similar results obtained by different gene or receptor manipulations might be simply the consequence of disrupting the pattern of activity.

Aging↗