PubMed Health⌕ Search

Biomedical subjects

Zhou Wang

Publications and source records attributed to Zhou Wang.

At least 19 recordsLinked to original sources
PubMed2007

The Hsp90 inhibitor, 17-AAG, prevents the ligand-independent nuclear localization of androgen receptor in refractory prostate cancer cells.

BACKGROUND: Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgen-refractory prostate cancer cells. METHODS AND RESULTS: We demonstrate increased nuclear localization of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells compared to parental androgen-sensitive human prostate cancer LNCaP cells. Analysis of AR mutants impaired in ligand-binding indicates that the nuclear localization of AR in C4-2 cells is truly androgen-independent. The hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA expression and disrupts the ligand-independent nuclear localization of AR at doses much lower than required to inhibit androgen-induced nuclear import. CONCLUSIONS: Hsp90 is a key regulator of ligand-independent nuclear localization and activation of AR in androgen-refractory prostate cancer cells.

Benzoquinones↗
PubMed2007

Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain.

BACKGROUND: U19/Eaf2 is an androgen-response gene and its downregulation is frequently observed in advanced human prostate cancer. U19/Eaf2 interacts with ELL, a fusion partner of MLL in the (11;19) (q23;p13.1) translocation in acute myeloid leukemia. U19/Eaf2 overexpression induces apoptosis and suppresses xenograft tumor growth. METHODS: Transfection and colony formation were used to assay for apoptosis and growth suppression of various U19/Eaf2 mutants. Co-immunoprecipitation was performed to test the interaction between the U19/Eaf2 constructs and ELL. RESULTS: The region of U19/Eaf2 essential for apoptosis and growth suppression was mapped to amino acids 68-113. This region was necessary and sufficient for binding ELL. Co-expression of U19/Eaf2 and ELL in 293 cells lead to significant increase in cell death and growth suppression. CONCLUSIONS: These observations argue that the interaction with ELL is essential for the induction of apoptosis and growth suppression by U19/Eaf2.

Apoptosis↗
PubMed2007

Microcatheter tip enhancement in fluoroscopy: a comparison of techniques.

We compared three techniques for enhancement of microcatheter tips in fluoroscopic images: conventional subtraction technique (CST); averaged image subtraction technique (AIST), which we have developed; and double average filtering (DAF) technique, which uses nonlinear background estimates. A pulsed fluoroscopic image sequence was obtained as a microcatheter was passed through a carotid phantom that was on top of a head phantom. The carotid phantom was a silicone cylinder containing a simulated vessel with the shape and curvatures of the internal carotid artery. The three techniques were applied to the images of the sequence, then the catheter tip was manually identified in each image, and 100 x 100 pixel images, centered at the indicated microcatheter tip positions, were extracted for the evaluations. The signal-to-noise ratio (SNR) was calculated in each of the extracted images from which the mean value of the SNR and its standard deviation (SD) were calculated for each technique. The mean values and the standard deviations were 4.36 (SD 3.40) for CST, 6.34 (SD 3.62) for AIST, and 3.55 (SD 1.27) for DAF. AIST had a higher SNR compared to CST in almost all frames. Although DAF yielded the smallest mean SNR value, it yielded the best SNR in those frames in which the microcatheter tip did not move between frames. We conclude that AIST provides the best SNR for a moving microcatheter tip and that DAF is optimal for a temporarily stationary microcatheter tip.

Carotid Artery, Internal↗
PubMed2006

Differential regulation of clusterin and its isoforms by androgens in prostate cells.

Clusterin mRNA levels were shown to increase dramatically in rat ventral prostate following castration, and clusterin was therefore originally thought to be repressed by androgens. It was later discovered that the increased clusterin levels are most likely due to castration-induced apoptosis of the prostatic epithelium rather than direct action of the androgen receptor (AR). In the studies presented here, LNCaP cells in culture and rat prostate organ culture were treated with androgens. Clusterin mRNA and protein are shown to increase with androgen treatment in a time- and dose-dependent manner. This induction of clusterin requires AR and can be inhibited by casodex, an AR antagonist. We have found that the first intron of the clusterin gene contains putative androgen response elements. The intronic region is shown to be bound by AR in chromatin immunoprecipitation assays and is transactivated by AR in reporter assays. Two isoforms of clusterin result from alternate transcriptional start sites. Both isoforms are cytoprotective; however, Isoform 1 has the capacity to produce a splice variant that is apoptotic. Real time PCR was used to determine the response of the two isoforms to androgens. Intriguingly, these results illustrated that Isoform 2 was up-regulated, whereas Isoform 1 was down-regulated by androgens. Isoform 2 was also increased as the LNCaP xenograft tumor progressed to androgen-independence, whereas Isoform 1 was unaltered. This androgen regulation of clusterin may underline the cytoprotective role of androgens in normal prostate physiology as well as play an antiapoptotic role in prostate cancer progression.

Alternative Splicing↗
PubMed2006

Regulation of calcium homeostasis by S100RVP, an androgen-regulated S100 protein in the rat ventral prostate.

BACKGROUND: S100RVP was previously identified as an androgen-response gene in the rat ventral prostate (RVP). Characterization of S100RVP is important for elucidating the function of S100 proteins in androgen action. METHODS: The expression and subcellular localization of S100RVP were determined by Northern blot, in situ hybridization, and fluorescent microscopy. Calcium overlay and calcium ionophore sensitivity assays were performed to investigate the calcium binding and function of S100RVP. RESULTS: S100RVP is abundantly expressed in the RVP epithelial cells. A green fluorescent protein(GFP)-S100RVP fusion protein is present in both the cytoplasm and nucleus of transfected cells. A GST-S100RVP fusion protein bound calcium in vitro at levels similar to known S100 proteins. Furthermore, GFP-S100RVP transfected LNCaP and PC3 cells exhibited reduced sensitivity to calcium ionophore-induced cell death, but not to UV-induced cell death. CONCLUSION: The results of this study argue for a role of S100RVP in calcium homeostasis in the prostate.

Animals↗
PubMed2006

Enhancement of intermittent androgen ablation by "off-cycle" maintenance with finasteride in LNCaP prostate cancer xenograft model.

BACKGROUND: Intermittent androgen ablation (IAA) was developed with the intention of delaying progression of prostate cancer to androgen-independence and improving quality of life. Our previous studies suggest that relative to dihydrotestosterone (DHT), testosterone (T) is a weak inducer of proliferation and a more potent inducer of differentiation. We hypothesize that administration of finasteride (F), a type-II 5-alpha-reductase inhibitor that increases T and decreases DHT, during the IAA "off-cycle" would enhance the efficacy. METHODS: After LNCaP tumor establishment, nude mice were castrated and randomized to continuous androgen ablation (CAA), continuous androgen ablation plus finasteride (CAA + F), intermittent androgen ablation (IAA), or intermittent androgen ablation plus finasteride (IAA + F). RESULTS: After one cycle of therapy, mice treated with IAA + F had significantly less tumor growth than the other treatment groups (P = 0.002). Mice treated with IAA + F had the best survival (P = 0.048) and were 3-5 times more likely to be alive 70 days following treatment initiation. CONCLUSIONS: IAA with finasteride provides the most favorable tumor growth kinetics and survival compared to both CAA and standard IAA.

Androgens↗
PubMed2006

ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation.

BACKGROUND: U19/Eaf2, an androgen-response gene, is downregulated in advanced human prostate cancer specimens and its overexpression can markedly induce apoptosis in prostate cancer cells. Eleven-nineteen Lysine-rich Leukemia (ELL) is an RNA polymerase II transcription elongation factor, initially identified as a fusion partner gene of MLL in the t(11; 19) (q23; p13.1) chromosomal translocation in acute myeloid leukemia. U19/Eaf2 was previously reported as an ELL-associated factor, a potential transcription factor binds to ELL, forming nuclear speckles in vivo. These findings suggest that ELL-U19/Eaf2 interaction is potentially important in prostate cancer progression and/or acute myeloid leukemia. However, the functional significance of U19/Eaf2 interaction with ELL remains unclear. METHODS: Using co-transfection, co-immunoprecipitation, protein stability assay and transactivation assay, we characterized the consequence of ELL binding to U19/Eaf2. RESULTS: We provide further evidence for U19/Eaf2 as a transcription factor and show that ELL binding is required for nuclear speckle formation of human U19/Eaf2, stabilizes U19/Eaf2 and enhances its transactivation activity. CONCLUSIONS: The above observations indicate ELL may be an important factor required for U19/Eaf2 function because U19/Eaf2 nuclear localization and transactivation activity are essential for its function as a transcription factor.

Base Sequence↗
PubMed2006

Quality-aware images.

We propose the concept of quality-aware image, in which certain extracted features of the original (high-quality) image are embedded into the image data as invisible hidden messages. When a distorted version of such an image is received, users can decode the hidden messages and use them to provide an objective measure of the quality of the distorted image. To demonstrate the idea, we build a practical quality-aware image encoding, decoding and quality analysis system, which employs: 1) a novel reduced-reference image quality assessment algorithm based on a statistical model of natural images and 2) a previously developed quantization watermarking-based data hiding technique in the wavelet transform domain.

Algorithms↗
PubMed2006

Investigation of gamma knife image registration errors resulting from misalignment between the patient and the imaging axis.

The ability of Leksell GammaPlan to perform stereotactic space localizations with image sets where there is misalignment of the patient's head (stereotactic frame and fiducial apparatus) relative to the computed tomography (CT) scanner coordinate system was studied. Misalignment is sometimes necessary for patient comfort. Results equally apply to magnetic resonance imaging. Seven 0.5 mm diameter CT-visible spheres were rigidly mounted to a string tied tightly at each end to diagonally opposite posts attached to a Leksell stereotactic frame. A standard CT fiducial box was applied to the frame in the usual clinical manner. A baseline CT scan (1 mm slice thickness) was obtained with the fiducial box perfectly aligned with the scanner axis. After localization of the image set, the (x,y,z) coordinate of the center of each sphere was recorded. Repeat CT scans with varying fiducial box misalignments with the imaging axis were subsequently obtained. The mean difference between the base line and the respective coordinates in misaligned geometries was approximately 0.2 mm (sigma=0.2 mm), well within the accuracy of the image sets and the delivery of radiosurgery with the Gamma Knife.

Artifacts↗
PubMed2006

[Recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy--a report of 196 cases].

BACKGROUND & OBJECTIVE: About one half of the patients with esophageal cancer may recur within 3 years after operation, but the recurrence pattern is still unclear. This study was to investigate the recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy. METHODS: Clinical data of 196 patients with squamous cell carcinoma of the middle third thoracic esophagus, who underwent Ivor-Lewis esophagectomy with two-field lymph node dissection from Jan. 1997 through Jan. 2001, were reviewed. The risk factors of postoperative recurrence within 3 years were analyzed with Logistic regressive model. RESULTS: Recurrence was recognized in 96 (48.9%) patients within 3 year after operation. The median time to recurrence was 12.2 months. Of the 96 cases of recurrence, 52 (54.1%) were locoregional, including 41 cases (78.8%) of mediastinal lymph node metastasis, and 8 cases (15.3%) of single cervical lymph node metastasis; 44 (45.8%) were hematogenous, including 10 cases of locoregional-hematogenous recurrence, and mainly located at liver, bone, and lung (39, 88.6%). The locoregional recurrence rate was significantly lower in the patients who received postoperative radiotherapy than in the patients have not received postoperative radiotherapy (23.3% vs. 41.3%, P<0.05). Logistic analysis showed that T3 and N1 tumor were independent risk factors of postoperative tumor recurrence. CONCLUSIONS: About one half of the patients would develop recurrent disease within 3 years after Ivor-Lewis esophagectomy, and most of them were with mediastinal lymph node, liver, bone, or lung metastasis. Postoperative radiotherapy is helpful to control locoregional recurrence.

Adult↗
PubMed2005

Timing is everything: preclinical evidence supporting simultaneous rather than sequential chemohormonal therapy for prostate cancer.

PURPOSE: Androgen ablation is the mainstay of systemic therapy for prostate cancer, with cytotoxic therapies reserved for hormone-refractory disease. It is not clear, however, that this is the most appropriate sequence of interventions for this disease. This study addresses the ideal timing of systemic treatments in the Shionogi and LNCaP xenograft models. We explored the hypothesis that stress-induced gene expression changes after chemotherapy can induce a hormone-independent phenotype. EXPERIMENTAL DESIGN: Three groups of mice bearing either Shionogi or LNCaP xenografts were treated with (a) initial castration and delayed paclitaxel, (b) initial paclitaxel and delayed castration, or (c) simultaneous castration plus paclitaxel. End points were time to tumor progression and time to sacrifice. Microarray and reverse transcription-PCR analyses were carried out to assess changes in gene expression induced by paclitaxel. RESULTS: Mice receiving simultaneous therapy showed a significant improvement in median time to progression (TTP: Shionogi, 65 versus 38 days, P = 0.004; LNCaP, 105 versus 70 days, P = 0.032) and time to sacrifice (Shionogi, 83 versus 66 days, P < 0.014) versus best sequential therapy. A marked lack of response to castration was observed after initial paclitaxel therapy. Gene expression and reverse transcription-PCR studies confirmed that several genes known to play a role in androgen independence were up-regulated in response to paclitaxel exposure. CONCLUSIONS: In laboratory models of prostate cancer, simultaneous androgen deprivation plus paclitaxel is more effective than sequential treatments. These findings provide preclinical proof-of-principle for ongoing clinical trials addressing the role and timing of systemic therapies in prostate cancer.

Androgens↗
PubMed2005

Contrast settling in cerebral aneurysm angiography.

During angiography, blood flow is visualized with a radiopaque contrast agent, which is denser than blood. In complex vasculature, such as cerebral saccular aneurysms, the density difference may produce an appreciable gravity effect, where the contrast material separates from blood and settles along the gravity direction. Although contrast settling has been occasionally reported before, the fluid mechanics behind it have not been explored. Furthermore, the severity of contrast settling in cerebral aneurysms varies significantly from case to case. Therefore, a better understanding of the physical principles behind this phenomenon is needed to evaluate contrast settling in clinical angiography. In this study, flow in two identical groups of sidewall aneurysm models with varying parent-vessel curvature was examined by angiography. Intravascular stents were deployed into one group of the models. To detect contrast settling, we used lateral view angiography. Time-intensity curves were analysed from the angiographic data, and a computational fluid dynamic analysis was conducted. Results showed that contrast settling was strongly related to the local flow dynamics. We used the Froude number, a ratio of flow inertia to gravity force, to characterize the significance of gravity force. An aneurysm with a larger vessel curvature experienced higher flow, which resulted in a larger Froude number and, thus, less gravitational settling. Addition of a stent reduced the aneurysmal flow, thereby increasing the contrast settling. We found that contrast settling resulted in an elevated washout tail in the time-intensity curve. However, this signature is not unique to contrast settling. To determine whether contrast settling is present, a lateral view should be obtained in addition to the anteroposterior (AP) view routinely used clinically so as to rule out contrast settling and hence to enable a valid time-intensity curve analysis of blood flow in the aneurysm.

Algorithms↗
PubMed2005

Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin.

Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC(50) (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38.

Adrenomedullin↗
PubMed2005

[Determination of rare earth elements in fetal kidney and cerebella by microwave dissolution and inductively coupled plasma-MS spectrometry].

OBJECTIVE: Study the contents of rare earth elements in normal fetal kidney and cerebella, and provide base data for the levels of rare earth elements in different phase of human development. METHODS: The samples were digested by closed-vessel microwave HNO3 + H2O2 dissolution system and directly tested by ICP-MS for the contents of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu in normal fetal kidney and cerebella. RESULTS: La mainly existed in fetal kidney (0.420 microg/kg), Ce mainly existed in fetal cerebella(0.363 microg/kg). Yb was little in both kidney and cerebella (0.103 microg/kg and 0.098 microg/kg). The contents of light rare earth elements in fetal kidney and cerebella were 1.427 microg/kg and 1.236 microg/kg, the contents of medium rare earth elements in fetal kidney and cerebella were 0.469 microg/kg and 0.432 microg/kg, and the contents of heavy rare earth elements in fetal kidney and cerebella were 1.387 microg/kg and 1.418 microg/kg. CONCLUSION: The rare earth elements all can be tested in fetal kidney and cerebella.

Cerebellum↗
PubMed2004

Adrenomedullin inhibits prostate cancer cell proliferation through a cAMP-independent autocrine mechanism.

Adrenomedullin (AM) is a multifunctional peptide expressed in the normal and malignant prostate, and in prostate cancer cells. To elucidate the potential role of AM in prostate cancer, we have transfected the human AM gene into PC-3, DU 145, and LNCaP prostate cancer cells. Northern blot, Western blot, and radioimmunoassay techniques confirmed an increase in the synthesis and secretion of the 6kDa mature peptide, in the AM-transfected clones. Proliferation and cell cycle assays demonstrated that AM overexpression inhibited cell proliferation in PC-3 and LNCaP cells through a G0/G1 cell cycle arrest, but not in DU 145 cells. In vivo growth assays also confirmed that, at least in PC-3, AM produced a very significant reduction of tumor volume. In addition, the three cell lines expressed the CL/RCP/RAMP-2 receptor complex by RT-PCR, which suggests that AM peptide acts through an autocrine loop in prostate cancer cells. Although cAMP elevation is the most common pathway involved in AM signalling, stimulation of PC-3, DU 145, and LNCaP with synthetic AM did not increase intracellular cAMP. However, short-term stimulation of PC-3 cells with synthetic AM increased ERK1/2 activation. On the contrary, long-term stimulation, or AM overexpression, caused a reduction in the basal activation of ERK1/2. In summary, our results demonstrate that AM (either overexpressed or exogenously added) causes an inhibition of prostate cancer cell growth. This inhibition does not depend on changes in intracellular cAMP levels, but may be related to ERK1/2 activation.

Adrenomedullin↗
PubMed2004

Identification and characterization of PLZF as a prostatic androgen-responsive gene.

BACKGROUND: Promyelocytic leukemia zinc finger protein (PLZF) was initially identified by virtue of its fusion with RARalpha as a result of a variant t(11;17) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia (APL) patients. PLZF has been reported to have pro-apoptotic and anti-proliferative activity both in vivo and in vitro. METHODS: Using a modified subtractive hybridization, we identified PLZF as an androgen-responsive gene in the rat ventral prostate. Northern blot and Western blot were used to characterize the regulation of PLZF by androgens in LNCaP cells. Stable transfections of PLZF in LNCaP cells were performed to assay the effect of PLZF overexpression on LNCaP cell proliferation. RESULTS: PLZF mRNA was transiently up-regulated by androgens in the regressed ventral prostate of castrated adult rat. PLZF was also up-regulated by androgens, at both mRNA and protein levels, in the androgen-responsive human prostate cancer cell line LNCaP. Androgen induction of PLZF mRNA was not inhibited by protein synthesis inhibitor cycloheximide but inhibited by androgen receptor antagonist bicalutamide, indicating that PLZF is a direct androgen-responsive gene. To study the functions of PLZF in androgen action, LNCaP sublines stably overexpressing PLZF were generated. PLZF overexpression inhibited LNCaP proliferation either in the presence or absence of androgen, which is consistent with the reported anti-proliferative activity of PLZF. CONCLUSIONS: The above observations indicate that PLZF is an androgen-responsive gene with anti-proliferative activity in prostate cancer cells.

Androgens↗
PubMed2004

[A study of correlation between early postoperative relapse with lymph node micrometastasis in patients with N0 esophageal cancer].

OBJECTIVE: To explore the correlation between early postoperative tumor relapse with lymph node micrometastasis in the patients with pN(0) esophageal cancer. METHODS: Using reverse transcriptase-polymerase chain reaction (RT-PCR), one hundred and sixty-six regional lymph nodes obtained from forty-three patients with esophagus cancer without invasion of the tumor confirmed by histopathologic analysis (pN(0)) were studied for further detecting mRNA of Mucin1 (MUC1) gene and determining nodal micrometastasis. All the patients underwent radical resection and regional lymph node dissection. Patients were followed up for one year to detect early tumor relapse. Difference in relapse was compared by chi(2) test. RESULTS: MUC1 mRNA expression was identified for twenty-six lymph nodes (15.7%), in eighteen patients (42%) who were diagnosed as having nodal micrometastasis. TNM staging for these patients was up-regulated from stages I-II(A) to stages II(B)-III. Relapse disease was found in nine patients with lymph nodes micrometastasis and three patients without nodal micrometastasis (P < 0.05). CONCLUSION: Early tumor relapse after radical surgery in the patients with pN(0) esophageal cancer might be correlated with nodal micrometastasis.

Esophageal Neoplasms↗