Biomedical subjects

Zhou Wang

Publications and source records attributed to Zhou Wang.

At least 37 records · Page 2Linked to original sources

PubMed2004

Gadd45gamma is androgen-responsive and growth-inhibitory in prostate cancer cells.

In our previous microarray analysis searching for genes differentially regulated by androgens in the rat ventral prostate, we identified GADD45gamma (growth arrest and DNA damage inducible, gamma) as one of the genes up-regulated by androgens. GADD45gamma was initially identified to be a gene involved in negative growth control and its overexpression induced cycle arrest and apoptosis in vitro. In this study, we showed that GADD45gamma was transiently up-regulated by androgens in the androgen-responsive human prostate cancer cell line LNCaP. The GADD45gamma up-regulation was blocked by an androgen receptor (AR) antagonist, bicalutamide, suggesting the involvement of the androgen receptor. However, this up-regulation was inhibited by cycloheximide, indicating that GADD45gamma induction by androgens requires new protein synthesis. Overexpression of GADD45gamma inhibited cell growth of LNCaP and PC3 cells and resulted in dramatic morphological changes in both cell lines, arguing that GADD45gamma is likely to participate in the differentiation program induced by androgens in the prostate. The above observations provide evidence that GADD45gamma is an androgen-responsive gene with growth-inhibitory activity in human prostate cancer cells.

Androgens↗

PubMed2004

Pigment epithelium-derived factor, a human testis epididymis secretory product, promotes human prostate stromal cell growth in culture.

PURPOSE: We identified and characterized unrecognized testicular secretory proteins that impact human prostate growth. MATERIALS AND METHODS: Human spermatocele fluid served as a source of testicular epididymal secretions and prostatectomy specimen benign prostatic hyperplasia stromal cells as the in vitro prostate growth promoting effects indicator. RMPI plus medium supplemented with 10% fetal bovine serum MALDI-TOF, MS FBS and ITS+ (Collaborative Research-Becton Dickinson, Bedford, Massachusetts) served as positive and negative controls, respectively. Whole and fractionated spermatocele fluid or specific proteins without and with select polyclonal or monoclonal antibodies were added to routine 6-day cultures. The observation of significantly increased 6-day cell counts compared with appropriate controls (p <0.05) was judged to reflect cell growth. Amino acid microsequencing and MALDI-TOF MS sequence analysis were done on persistent protein bands from active spermatocele fluid fractions. RESULTS: Whole and fractionated human spermatocele fluid increased stromal cell culture numbers significantly. Sequence analysis of 47 and 17 kDa 1-dimensional gel bands in the final active fraction identified a major peptide with sequence homology to human pigment epithelium-derived factor (PEDF). The presence of PEDF was confirmed by Western blot analysis. Addition of recombinant PEDF to incomplete medium significantly increased stromal cell culture number. PEDF antibodies neutralized or markedly decreased the stromal stimulating effect of spermatocele fluid and PEDF. CONCLUSIONS: The observations presented provide evidence for human testis/epididymis secretion of PEDF and for a PEDF in vitro growth promoting effect on benign prostatic hyperplasia stroma. The concept that testicular epididymal secretory proteins may influence normal and abnormal prostate growth warrants continued consideration.

Body Fluids↗

PubMed2004

Image quality assessment: from error visibility to structural similarity.

Objective methods for assessing perceptual image quality traditionally attempted to quantify the visibility of errors (differences) between a distorted image and a reference image using a variety of known properties of the human visual system. Under the assumption that human visual perception is highly adapted for extracting structural information from a scene, we introduce an alternative complementary framework for quality assessment based on the degradation of structural information. As a specific example of this concept, we develop a Structural Similarity Index and demonstrate its promise through a set of intuitive examples, as well as comparison to both subjective ratings and state-of-the-art objective methods on a database of images compressed with JPEG and JPEG2000.

Algorithms↗

PubMed2004

Measurement of flow modification in phantom aneurysm model: comparison of coils and a longitudinally and axially asymmetric stent--initial findings.

Dye-dilution imaging sequences were performed and time-density curves were constructed in elastomer vessel aneurysm models to demonstrate the effectiveness of coils and an asymmetric stent in disrupting standard vortex flow. Compared with the use of coils, the use of stents led to marked flow modification, as seen with imaging sequences, and substantially slower inflow, as indicated by time-density curves, owing to the low-porosity region of the stent that covers the aneurysm orifice. These flow examination results indicate that potentially favorable flow modification features can be created by using the described asymmetric stent design, the use of which may lead to alternative methods of image-guided endovascular cerebral aneurysm therapy.

Blood Vessel Prosthesis Implantation↗

PubMed2003

Identification and characterization of an androgen-responsive gene encoding an aci-reductone dioxygenase-like protein in the rat prostate.

The ALP1 [aci-reductone dioxygenase (ARD)-like protein 1] gene was identified in a comprehensive cDNA subtraction aimed at identifying genes regulated by androgens in the rat ventral prostate. ALP1 is homologous to the ARD/ARD' that were discovered in Klebsiella pneumoniae as enzymes that have the same polypeptide sequence and differ only in their metal content. This family of proteins is evolutionarily conserved from bacteria to humans and is involved in the methionine salvage pathway. Northern and Western blot confirmed the regulation of ALP1 by androgens in the rat ventral prostate. ALP1 mRNA is expressed in a variety of tissues; however, its regulation by androgens was specific to the prostate. ALP1 is expressed by the glandular epithelial cells of the rat prostate, with little or no expression in the stromal cells. ALP1 is down-regulated in the different rat Dunning tumor cell lines compared with the normal or castrated rat prostate. Expression studies showed that ALP1 overexpression is not tolerated by AT6.1 cells. Further studies demonstrated that ALP1 is also down-regulated in the human prostate cancer cell lines LNCaP, PC3, and DU145, and overexpression induces cell death in these cells. Taken together, our observations suggest that ALP1 may have an important role in androgen regulated prostate homeostasis as well as in prostate cancer progression by regulating cell death of prostate cancer cells.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor.

Androgen receptor (AR) belongs to the steroid receptor superfamily that regulates gene expression in a ligand-dependent fashion. AR is localized to the cytoplasm in the absence of androgen and translocates into the nuclei to activate gene expression in the presence of ligand. Regulation of AR nuclear import and export represents an essential step in androgen action. A nuclear localization signal (NLS) has been identified in the DNA-binding domain and hinge region of AR and other steroid receptors. Studies on nuclear export of AR, however, are limited, and what might be the underlying mechanism regulating the intracellular localization of steroid receptors is unclear. Our studies have identified a leptomycin B-insensitive nuclear export signal (NESAR) in the ligand-binding domain of AR, which is active in the absence of androgen and repressed upon ligand binding. Consistent with its androgen-sensitivity, NESAR contains amino acid residues in the immediate vicinity of the bound ligand. NESAR is necessary for AR nuclear export and is dominant over the NLS in the DNA-binding domain and hinge region in the absence of hormone. Our findings suggest that androgen can regulate NESAR and, subsequently, the NLS of the AR, providing a mechanism by which androgen regulates AR nuclear/cytoplasmic shuttling. Estrogen receptor alpha and mineralocorticoid receptor also contain functional NES, suggesting that this ligand-regulated NES is conserved among steroid receptors.

Active Transport, Cell Nucleus↗

PubMed2003

Suppression of prostate tumor growth by U19, a novel testosterone-regulated apoptosis inducer.

Androgens control prostate homeostasis and regulate androgen response genes. Here, we report the identification and characterization of U19, a novel testosterone-regulated apoptosis inducer with tumor suppressive activity. U19 is an evolutionarily conserved protein expressed in many human tissues, with the most abundant expression in the prostate, bone marrow, kidney, and lymph nodes. Overexpression of U19 in 12 surveyed cell lines induced apoptosis, and new protein synthesis is required for apoptosis induction. Expression of U19 in xenograft prostate tumors markedly induced apoptosis and inhibited tumor growth in vivo. Consistent with its tumor-suppressive role, U19 down-regulation was observed in all of the surveyed prostate cancer cell lines and in 19 of 23 clinical human prostate tumor specimens. Loss of heterozygosity analysis revealed U19 allelic loss in 19 of the 23 specimens. Furthermore, two of the specimens had homozygous U19 deletions, and one specimen had hypermethylated U19 promoter, indicating that U19 can be inactivated genetically or epigenetically. These observations suggest that U19 is growth inhibitory and tumor suppressive and that the disruption of androgen-dependent growth inhibition via U19 down-regulation is commonly associated with prostate cancer progression.

Amino Acid Sequence↗

PubMed2003

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo.

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959+/-0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G(1)/G(0) cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

Adrenomedullin↗

PubMed2003

Vessel size measurements in angiograms: manual measurements.

Vessel size measurement is perhaps the most often performed quantitative analysis in diagnostic and interventional angiography. Although automated vessel sizing techniques are generally considered to have good accuracy and precision, we have observed that clinicians rarely use these techniques in standard clinical practice, choosing to indicate the edges of vessels and catheters to determine sizes and calibrate magnifications, i.e., manual measurements. Thus, we undertook an investigation of the accuracy and precision of vessel sizes calculated from manually indicated edges of vessels. Manual measurements were performed by three neuroradiologists and three physicists. Vessel sizes ranged from 0.1-3.0 mm in simulation studies and 0.3-6.4 mm in phantom studies. Simulation resolution functions had full-widths-at-half-maximum (FWHM) ranging from 0.0 to 0.5 mm. Phantom studies were performed with 4.5 in., 6 in., 9 in., and 12 in. image intensifier modes, magnification factor = 1, with and without zooming. The accuracy and reproducibility of the measurements ranged from 0.1 to 0.2 mm, depending on vessel size, resolution, and pixel size, and zoom. These results indicate that manual measurements may have accuracies comparable to automated techniques for vessels with sizes greater than 1 mm, but that automated techniques which take into account the resolution function should be used for vessels with sizes smaller than 1 mm.

Anatomy, Cross-Sectional↗

PubMed2003

Identification of androgen-responsive genes in the rat ventral prostate by complementary deoxyribonucleic acid subtraction and microarray.

We have reported the identification of approximately two dozen androgen-responsive genes, on the basis of their induction by androgens in the castrated rat ventral prostate, using PCR-based subtractive hybridization. The same prostatic cDNA samples were subjected to a modified subtractive hybridization, resulting in the identification of 21 new androgen-responsive genes, of which 14 were known and 7 were novel genes. To complement our subtraction study, we have used an Incyte rat cDNA microarray, consisting of 8951 known genes and expressed sequence tags, and found that 162 genes were up-regulated and 143 genes were down-regulated 2.3-fold or more by androgens. As expected, the genes isolated from our subtraction overlap with genes found with microarray. Northern blot was carried out on all of the genes identified by subtraction and a few selected genes from microarray. All of the assayed genes are regulated by androgens, validating our subtraction and microarray studies. The identified genes can be classified into several functional groups, including metabolism, protein chaperoning and trafficking, protein synthesis, secretions, cell cycle and apoptosis, structural and extracellular matrix proteins, and novel proteins. Identification of these androgen-responsive genes will contribute to the understanding of androgen action in the normal and cancerous prostate.

Androgens↗

PubMed2003

Effect of gastrin on differentiation of rat intestinal epithelial cells in vitro.

AIM: To investigate the effect of gastrin on differentiation of IEC-6 cell line in vitro. METHODS: IEC-6 cells were incubated with gastrin. On day 7 after treatment, cell morphology was examined by light microscope, and on day 20, the cellular ultrastructures were examined by electron microscope. After exposure to gastrin for 6 hours, villin mRNA was analyzed by reverse transcription-polymerase chain reaction, and on day 7, the expression of villin was examined by immunocytochemical analysis with laser confocal microscope. RESULTS: After exposure to gastrin, IEC-6 cells showed differentiated phenotypes as villas enterocytes and contained an abundance of plasma, small nuclei with nucleoli, and were arranged regularly. There were numerous microvilli around edge of the cells, and several cells showed columnar structures. Villin mRNA expression in cytoplasm was increased in comparison with control. CONCLUSION: Differentiated characteristics of villus enterocytes and phenotypic changes of rat intestinal epithelial cells (IEC-6) are induced by gastrin, and the effects of gastrin are correlated to increased villin expression.

Animals↗

PubMed2003

[Protective effects of green tea on mice with the irradiating damage induced by gamma-ray].

OBJECTIVE: To evaluate the protective effects of green tea on mice with the irradiating damage induced by 60Co-gamma-ray. METHODS: Thirty-five mice were divided into normal control group, irradiating control group and three experiment groups. The mice of the experiment groups drank in water soluble extractives of green tea (1.25%, 2.5%, 5%) for two weeks. Then all animals were irradiated by 60Co-gamma-ray except those of the normal control group. The animals of three experiment groups continued drinking the water soluble extractives of green tea for one week, after that all mice of the five groups were killed. The levels of malondiadehyde (MDA) and the activities of superoxide dismutase (SOD) in serums, the optical density (OD) value of DNA and the number of karyota of femur, the frequency of micronuclei in polychromatophilic erythrocytes of bone marrow in mice of all groups were measured. RESULTS: Compared with the measurements in the irradiating control group, the level of MDA in serums and the frequency of micronuclei in polychromatophilic erythrocytes of bone marrow in the three experiment groups were decreased significantly (P < 0.05), while the activities of SOD in serums, the OD value of DNA and the number of karyota of femur in mice of the three experiment groups were increased significantly (P < 0.05). CONCLUSION: The water soluble extractives of green tea have protective effects on mice with the irradiating damage induced by gamma-ray.

Animals↗

PubMed2003

Lymph node occult micrometastasis in patients with non-small cell lung carcinoma: genetic diagnosis and its impact on prognosis.

BACKGROUND & OBJECTIVE: Occult micrometastasis to mediastinal lymph node, which could not be detected by routinely histopathologic examination, might be correlated with the prognosis of patients with non-small cell lung carcinoma (NSCLC). The aim of this stud y was to diagnose occult micrometastasis of mediastinal lymph node in NSCLC patients and evaluate its prognostic significance. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), 242 stations of mediastinal lymph nodes, which were free of tumor determined by histopathologic examination(pN0), from 58 patients were examined for MUC1 gene mRNA and to diagnose occult micrometastasis. All the patients were followed-up for three years. The survival rate was calculated by Kaplan-Meier method and the survival was compared with log-rank test between the patients with and without occult nodal micrometastasis. RESULTS: The MUC1 gene mRNA was identified in 23 stations of lymph nodes from 16 patients, and nodal occult micrometastasis was diagnosed in the 27.6% of the patients. TNM staging for these patients was up-regulated from stageI(A)-II(B) to stage III(A). The 3-year survival rate in the patients with nodal occult micrometastasis (43.7%) was lower than that in the patients without nodal occult micrometastasis (73.8%) (P< 0.05). CONCLUSION: The expression of MUC1 gene mRNA in mediastinal lymph node is associated with poor prognosis of NSCLC patients with pN0 disease, suggesting that it may be an indicator of poor prognosis.

Adult↗

PubMed2003

[Expression of CGRP, ACTH and 5-HT in normal human lymph nodes].

AIM: To detect the expression of calcitonin-gene-related peptide (CGRP), adrenocorticotropin (ACTH), and serotonin (5-HT) in normal human lymph nodes and explore their influences on immune system. METHODS: The expression of CGRP, ACTH and 5-HT in the lymph nodes, including proliferative lymph nodes, were detected by SABC Immunohistochemical staining. RESULTS: In 35 cases of lymph node specimens, the positive rates of CGRP, ACTH and 5-HT expression were 88.5%(31/35), 85.4%(30/35) and 94.2%(33/35) respectively. These 3 molecules had a similar distribution in germinal center of lymph nodes, mainly in the cells of paracortical region, the cells in germinal center of lymph follicles and macrophages, etc. CONCLUSION: There are considerably high positive rates of CGRP, ACTH and 5-HT in human peripheral lymph nodes, and their distribution area are basically coincident with that of immunocytes in the lymph nodes.

Adrenocorticotropic Hormone↗

PubMed2002

Adrenomedullin and proadrenomedullin N-terminal 20 peptide in the normal prostate and in prostate carcinoma.

There is increasing evidence for the important role played by regulatory peptides in the physiology of the normal and neoplastic prostate. Adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP) are recently discovered regulatory peptides widely expressed in the normal prostate and in prostate carcinoma. AM is produced in secretory, stroma, and endothelial cells and in neurons of the prostate ganglia. PAMP is only produced by neuroendocrine cells. The expression of AM mRNA is regulated by androgens in the rat prostate. The number of neuroendocrine cells expressing PAMP is increased in prostate carcinoma after androgen deprivation, which shows that this peptide could regulate androgen-independent prostate tumor growth. However, the roles of AM and PAMP in the normal prostate and in prostate carcinoma are yet to be elucidated.

Adrenomedullin↗

PubMed2002

Androgen regulation of spermidine synthase expression in the rat prostate.

BACKGROUND: Spermidine synthase, an essential enzyme in the polyamine synthesis pathway, was identified as one of the androgen-response genes in the rat ventral prostate. Characterization of androgen regulation of spermidine synthase is important to the understanding of androgenic regulation of polyamine synthesis. METHODS: Full-length cDNA encoding rat spermidine synthase was isolated from a lambdaZAP cDNA phage library. Young male adult Sprague-Dawley rats were used for castration and androgen replacement. Northern blot and in situ hybridization were used to characterize gene expression. RESULTS: The amino acid sequence of rat spermidine synthase shares 99% and 94% identity with that of mouse and human spermidine synthase, respectively. Spermidine synthase gene is abundantly expressed and regulated by androgens in the ventral, dorsal, and lateral lobes of the rat prostate, and its expression is localized to the epithelial cells. Spermidine synthase also is regulated by androgens in the seminal vesicles but not in the muscle, brain, kidney, thymus, heart, or liver, suggesting that this enzyme is responsive to androgen in the male sex accessory organs only. The expression of spermidine synthase and two other enzymes involved in polyamine synthesis, S-adenosylmethionine decarboxylase and ornithine decarboxylase, are regulated by androgens coordinately. CONCLUSIONS: Spermidine synthase is most abundantly expressed and regulated by androgens in the prostatic epithelial cells, suggesting that regulation of spermidine synthase is likely a key step in coordinated androgen regulation of polyamine synthesis in the prostate.

Adenosylmethionine Decarboxylase↗

PubMed2002

Vessel size measurements in angiograms: a comparison of techniques.

As interventional procedures become more complicated, the need for accurate quantitative vascular information increases. In response to this need, many commercial vendors provide techniques for measurement of vessel sizes, usually based on derivative techniques. In this study, we investigate the accuracy of several techniques used in the measurement of vessel size. Simulated images of vessels having circular cross sections were generated and convolved with various focal spot distributions taking into account the magnification. These vessel images were then convolved with Gaussian image detector line spread functions (LSFs). Additionally, images of a phantom containing vessels with a range of diameters were acquired for the 4.5", 6", 9", and 12" modes of an image intensifier-TV (II-TV) system. Vessel sizes in the images were determined using a first-derivative technique, a second-derivative technique, a linear combination of these two measured sizes, a thresholding technique, a densitometric technique, and a model-based technique. For the same focal spot size, the shape of the focal spot distribution does not affect measured vessel sizes except at large magnifications. For vessels with diameters larger than the full-width-at-half-maximum (FWHM) of the LSF, accurate vessel sizes (errors approximately 0.1 mm) could be obtained by using an average of sizes determined by the first and second derivatives. For vessels with diameters smaller than the FWHM of the LSF, the densitometric and model-based techniques can provide accurate vessel sizes when these techniques are properly calibrated.

Angiography↗

PubMed2002

Improved method of magnification factor calculation for the angiographic measurement of neurovascular lesion dimensions.

Accurately evaluating the size of a neurovascular lesion is essential for properly devising treatment strategies. The magnification factor must be considered in order to measure the dimension of a lesion from an angiogram. Although a method to calculate the magnification of the lesion by linear interpolation of the measurable magnification factors of two markers has been in use, this paper shows that it can be inaccurate. By deriving the exact formula for calculating the magnification factor at the level of the lesion, the error generated by the linear interpolation of magnification factor has been evaluated. This error was found to depend on source-to-skin distance (SSD), the location of the lesion in the head, and the head size. The closer the head is to the focal spot and the nearer the lesion is to the center of the head, the larger is the error. Since clinicians tend to use high geometric magnification (i.e., small SSD) in interventional procedures, there exists a possible consequential error of more than 3% in lesion sizing if the linear-interpolation calculation method is used. It is thus recommended that the exact formula derived here be used to calculate the magnification factor to improve accuracy.

Aneurysm↗