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Wei Hu

Publications and source records attributed to Wei Hu.

At least 73 records · Page 4Linked to original sources
PubMed2005

Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer.

The STK15 (also known as Aurora-A/BTAK) gene localized on chromosome 20q13 and encoding a centrosome-associated serine/threonine kinase is amplified and overexpressed in multiple human tumor cell types. Overexpression of this gene is involved in tumorigenic transformation, induction of centrosome duplication-distribution abnormalities, and aneuploidy in mammalian cells. To examine the potential role of STK15 in ovarian tumorigenesis, its mRNA and protein expression status were examined in cells grown in culture from 15 ovarian cancer specimens using semiquantitative RT-PCR and Western blot analysis. Normal ovarian surface tissues and the near diploid nontumorigenic breast epithelial cell line MCF10 were used as controls. The status of STK15 correlated with transformation-associated cellular phenotypes including tumorigenicity in nude mice, p53 expression level, and chromosomal ploidy. For chromosome ploidy analyses, FISH was carried out with direct fluorescence-labeled a-satellite probes for chromosome 3 and 17. STK15 mRNA was found overexpressed in 10 of the 15 ovarian cancer cell cultures. Five of these cell cultures revealed a truncated form of the STK15 protein with a molecular mass of 36 kDa. When tested for tumorigenicity in nude mice, 9 of the 10 cell cultures that overexpressed STK15 mRNA formed tumors in nude mice, while only one of the five cell cultures with no overexpression did. Cells overexpressing STK15 mRNA showed significant correlation with chromosome 3 polysomy. Six of the 13 (46%) cell cultures analyzed for p53 expression revealed overexpression of p53 and five of these six (83%) also overexpressed STK15. Four of the remaining seven cultures (57%) with overexpression of STK15 revealed minimal or no expression of p53. These results demonstrate that overexpression of STK15 significantly correlates with nude mice tumorigenicity and chromosomal aneuploidy in human ovarian cancer cells grown in vitro. Additionally, cells overexpressing STK15 also revealed frequent coordinate loss of wild-type p53 function manifested either as highly expressed intense staining reflective of a mutant form of p53 or almost complete absence of p53 staining. Overexpression of STK15 with coordinate loss of wild-type p53 function thus appears to play an important role in ovarian tumorigenesis and offers a novel molecular target in designing effective therapy of human ovarian cancer.

Aneuploidy↗
PubMed2005

Food and botanical groupings and risk of breast cancer: a case-control study in Shanghai, China.

Breast cancer incidence rates more than double in Chinese women as they migrate from China to Hong Kong to the United States, suggesting that environmental factors contribute to the international variation in breast cancer incidence. Several dietary factors, which differ between the United States and the Chinese population, including intake of soy, meat, and fruits and vegetables, have been suggested to affect breast cancer risk. This report describes results from a case-control study of diet and risk of breast cancer nested in a randomized trial of breast self exam in Shanghai, China. Participating breast cancer cases (n = 378) and frequency age-matched controls (n = 1,070) completed a comprehensive food frequency questionnaire and a risk factor questionnaire. After adjustment for age, total energy intake, and total years of breast-feeding, women in the highest quartile of fruit and vegetable intake (> or =3.8 servings/d) were significantly less likely to have breast cancer (odds ratio, 0.48; 95% confidence interval, 0.29-0.78) as compared with women in the lowest quartile of intake (< or =2.3 servings/d). Egg consumption was also significantly inversely associated with risk of breast cancer (odds ratio for > or =6.0 eggs/wk versus < or =2.0 eggs/wk is 0.56; 95% confidence interval, 0.35-0.91). There was no difference in soy consumption between cases and controls. None of the associations with a single botanical family explained the strong inverse relationship between fruits and vegetables and breast cancer risk. These results provide additional evidence in support of the important role of fruits and vegetables in breast cancer prevention.

Adult↗
PubMed2005

[Vascular endothelial growth factor expression and microvessel density in stage I-II non-small cell lung cancer and their prognostic significances].

BACKGROUND & OBJECTIVE: TNM staging system is used widely to predict prognosis of non-small cell lung carcinoma (NSCLC) patients, but patients with the same stage may have very different survivals; better prognostic index is needed. Angiogenesis is considered to be essential for tumor development, progression, and metastasis, but the prognostic impacts of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in NSCLC is controversial. This study was to evaluate the prognostic value of VEGF and MVD in NSCLC. METHODS: VEGF and MVD in 214 specimens of stageI-II NSCLC (20 in stage IA, 137 in stage IB, and 57 in stage IIB) were detected by tissue chip and SP immunohistochemistry. No patient underwent postoperative antitumor treatment. RESULTS: VEGF expression didn't relate to gender, age, blood type, pathologic type, and TNM stage (P0.05). MVD correlated with age and pathologic type (P0.05), but did not relate to gender, blood type, and TNM stage (P0.05). The mean value of MVD was 65.8+/-5.2 in VEGF-low patients, and 67.5+/-2.5 in VEGF-high patients (P0.05). The 5-year survival rate was significantly lower in MVD-high patients than in MVD-low patients (34.5% vs. 60.0%, P=0.013). Furthermore, multivariate Cox regression analysis showed that MVD (P=0.000) was an independent prognostic factor of NSCLC. CONCLUSION: High MVD closely relates to poor prognosis of stageI-II NSCLC.

Adolescent↗
PubMed2004

Cytoplasmic impact on cross-genus cloned fish derived from transgenic common carp (Cyprinus carpio) nuclei and goldfish (Carassius auratus) enucleated eggs.

In previous studies of nuclear transplantation, most cloned animals were obtained by intraspecies nuclear transfer and are phenotypically identical to their nuclear donors; furthermore, there was no further report on successful fish cloning since the report of cloned zebrafish. Here we report the production of seven cross-genus cloned fish by transferring nuclei from transgenic common carp into enucleated eggs of goldfish. Nuclear genomes of the cloned fish were exclusively derived from the nuclear donor species, common carp, whereas the mitochondrial DNA from the donor carp gradually disappeared during the development of nuclear transfer (NT) embryos. The somite development process and somite number of nuclear transplants were consistent with the recipient species, goldfish, rather than the nuclear donor species, common carp. This resulted in a long-lasting effect on the vertebral numbers of the cloned fish, which belonged to the range of goldfish. These demonstrate that fish egg cytoplasm not only can support the development driven by transplanted nuclei from a distantly related species at the genus scale but also can modulate development of the nuclear transplants.

Animals↗
PubMed2004

Identification and characterization of an L-type Cav1.2 channel in spiral ligament fibrocytes of gerbil inner ear.

Intracellular free Ca2+ levels are critical to the activity of BK channels in inner ear type I spiral ligament fibrocytes. However, the mechanisms for regulating intracellular Ca2+ levels in these cells are currently poorly understood. Using patch-clamp technique, we have identified a voltage-dependent L-type Ca2+ channel in type I spiral ligament fibrocytes cultured from gerbil inner ear. With 10 mM Ba2+ as the conductive cation, an inwardly rectifying current was elicited with little inactivation by membrane depolarization. The voltage activation threshold and the half-maximal voltage activation were -40 and -6 mV, respectively. This inward whole-cell current reached its peak at around 10 mV of membrane potential. The amplitude of the peak current varied among cells ranging from 50 to 274 pA with an average of 132.4 +/- 76.2 pA (n = 19); 10(-6) M nifedipine significantly inhibited the inward currents by 90.3 +/- 1.2% (n = 11). RT-PCR analysis revealed that cultured type I spiral ligament fibrocytes express the alpha1C isoform of the L-type Ca2+ channels encoded by the Cav1.2 gene. The expression of this channel in gerbil inner ear was confirmed by RT-PCR analysis using freshly isolated spiral ligament tissues. The Cav1.2 channel may function in conjunction with a previously identified intracellular Ca-ATPase (SERCA) to regulate intracellular free Ca2+ levels in type I spiral ligament fibrocytes, and thus modulate BK channel activity in these cells.

Animals↗
PubMed2004

Rapid and improved method for windowing eggs accessing the stage X chicken embryo.

The chick stage X blastoderm is routinely accessed through a small window in a freshly laid egg. However, windowing severely compromises embryo survival with hatch rates as low as a few percent. We previously reported a simple modification to the standard method that reduced introduction of air into the sealed egg and improved the hatchability to 32%. Here, we describe an even simpler and more rapid method for sealing a windowed egg using hot glue or paraffin in which the hatch rate increased to an average of 63% of the unwindowed control eggs. The primary reason for low hatchability can be attributed to air trapped within the egg during windowing and/or leakage during incubation, as shown by increased lethality by artificially introducing air into windowed and sealed eggs. Although the hatch rate was considerably improved, air can still enter the egg during incubation and is likely to account for less than 100% hatchability of the sealed eggs. The success of this new windowing method will facilitate high throughput for the production of transgenic birds and find use in developmental biology, toxicity testing, and avian disease research.

Adhesives↗
PubMed2004

Dysregulation of the TGF-beta postreceptor signaling pathway in cell lines derived from primary or metastatic ovarian cancer.

Transforming growth factor-beta (TGF-beta) may cause cell cycle arrest, terminal differentiation, or apoptosis in most normal epithelial cells, whereas most malignant cell lines are resistant to TGF-beta. Mechanisms of resistance to TGF-beta caused by modulation of cell cycle regulators and/or inactivation of components of the TGF-beta signaling transduction pathway such as C-myc and Smad4 are not well understood. To investigate the potential association between loss of sensitivity to TGF-beta and expression status of transforming growth factor receptor II (TbetaR II) , Smad4, CDC25A and C-myc in 14 cell lines derived from ovarian cancer, the expression levels of these genes were detected by semi-quantitative RT-PCR. Normal ovarian surface tissues were used as controls. The expression of TbetaR II was detectable in all of 14 cell lines. The expression of Smad4 was decreased in 10 cell lines and 9 cell lines overexpressed CDC25A, as compared to normal controls. CDC25A gene was overexpressed with 88% (8/9) in tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non-tumorigenic cell lines (P<0.05). C-myc was not overexpressed in any of these cell lines. The loss of sensitivity to TGF-beta of cell lines derived from ovarian cancers may be related to a decreased expression of Smad4, which mediates TGF-beta induced growth inhibition, and/or an overexpression of CDC25A. This overexpression of CDC25A correlates with increased tumorigenicity of ovarian cancer cell lines. The loss of sensitivity to TGF-beta is not associated with a lack of TbetaR II.

Animals↗
PubMed2004

Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer.

GOALS: Resistance to cisplatin is the main reason for treatment failure in ovarian cancer. Apoptosis is the main mechanism of action of most cancer chemotherapeutic agents. The apoptosis-associated proteins expressed in cisplatin-sensitive (A2780, COC1) and -resistant (A2780/DDP, COC1/DDP) ovarian cancer cell lines, as well as their effects on caspase-3 activity in these cells, were studied by reverse transcriptase polymerase chain reaction and Western blot analysis. METHODS: The apoptotic ratios of A2780, COC1, A2780/DDP, and COC1/DDP cells after treatment with cisplatin were measured by flow cytometry. RESULTS: Expression of Bcl-2 and Bcl-X(L) in A2780/DDP and COC1/DDP cells was significantly higher than that in A2780 and COC1 cells, respectively. Expression of Bax and Bcl-Xs did not differ in cisplatin-resistant and -sensitive cells. Caspase-3 activity was reduced markedly and apoptotic ratios were significantly lower in A2780/DDP and COC1/DDP cells than in A2780 and COC1 cells after treatment with cisplatin. CONCLUSION: We conclude that overexpression of antiapoptotic proteins Bcl-2 and Bcl-X(L) and down-regulation of caspase-3 activity may be associated with cisplatin resistance in human ovarian cancer.

Antineoplastic Agents↗
PubMed2004

Proteomics in cancer screening and management in gynecologic cancer.

Biomarkers are used routinely for population screening, disease diagnosis and prognosis, monitoring of therapy, and prediction of therapeutic response. Unfortunately, most biomarkers have low sensitivity and specificity and little predictive value. Novel techniques for better screening and early diagnosis of ovarian cancer are urgently needed. Proteomics, the study of the cellular proteins and their activation states, integrates some fundamental techniques, including high-throughput protein purification and profiling, genomic and proteomic databases, and mass spectrometry. In oncology, proteomics will contribute greatly to our understanding of gene functions in tumor development and provide information in clinical applications. This article reviews proteomic techniques and their potential applications in gynecologic cancer screening and management.

Biomarkers, Tumor↗
PubMed2004

Using air pollution based community clusters to explore air pollution health effects in children.

To study respiratory health effects of long-term exposure to ambient air pollutant mixture, we observed 7058 school children 5-16 years of age living in the four Chinese cities of Lanzhou, Chongqing, Wuhan, and Guangzhou. These children were enrolled from elementary schools located in eight districts, one urban district and one suburban district in each of the above cities. Ambient levels of PM(2.5), PM(10-2.5), total suspended particles (TSP), SO(2), and NO(x) were measured in these districts from 1993 to 1996. Based on a cluster analysis of arithmetic mean concentrations of PM(2.5), PM(10-2.5), (TSP-PM(10)), SO(2), and NO(x), we classified these children into four ordinal categories of exposure to ambient air pollutant mixtures. We tested for exposure-response relationships using logistic regression models, controlling for relevant covariates. We observed monotonic, positive relationships of exposure to the pollutant mixture with prevalence rates of cough with phlegm and wheeze. Other outcomes were not associated with the exposure in a monotonic exposure-response pattern. Even so, odds ratios for cough, phlegm, bronchitis, and asthma in the higher exposure district clusters were all higher than in the lowest exposure district cluster. We found evidence that exposure to the pollutant mixtures had adverse effects on children living in the four Chinese cities.

Adolescent↗
PubMed2004

Schistosome transcriptomes: new insights into the parasite and schistosomiasis.

Schistosomiasis is one of the most serious parasitic diseases. More than 250 million people are infected with schistosomes in the tropics or subtropics. The parasitic flukes have some unique biological features: dioecism, complex life cycles, mechanisms to avoid host immune responses, and an apparent reliance on host endocrine and immune signals to complete their development, maturation and egg production. Recently, a large dataset of expressed sequence tags (ESTs) were generated from Schistosoma japonicum and Schistosoma mansoni, from which numerous novel genes were identified. The transcriptome analyses provide the basis for a comprehensive understanding of the molecular mechanisms involved in schistosome nutrition and metabolism, host-dependent development and maturation, immune evasion and invertebrate evolution. In addition, new potential vaccine candidates and drug targets have been predicted.

Animals↗
PubMed2004

Schistosome transcriptome analysis at the cutting edge.

We live in the era of post-genomics, a term that was, until recently, inappropriate when considering the blood flukes of humans because of the relative lack of knowledge of the schistosome genome. The position has, however, changed dramatically following the recent publication of two landmark papers on transcriptome analysis of Schistosoma japonicum and Schistosoma mansoni. In a quantum leap, both studies report on the identification of many novel genes and genes not previously known from schistosomes. The datasets provide new insights into the biology of the schistosomes and offer an opportunity for identification of potential antischistosome vaccine candidates and drug targets. Remarkable recent progress has also been achieved in genomic sequencing, and completed genomes for both species can be expected shortly.

Animals↗
PubMed2004

One- and two-dimensional solid-state magic angle spinning NMR studies on the hydration process of layered sodium disilicate SKS-6.

Three different kinds of silanols, which include isolated silanol, silanol I (with the hydroxyl proton bonded to an oxygen atom in the adjacent layer) and silanol II (with the hydroxyl proton bonded to the non-bridging oxygen at the same silicon atom), are generated during the hydration process of SKS-6 (delta-Na2Si2O5). 1H-1H nuclear Overhauser enhancement spectroscopy reveals that the proton of silanol I has an effective chemical exchange or spin diffusion with the proton of hydrogen-bonded water, while the proton of silanol II is likely far away from the other proton-containing species. 29Si magic angle spinning, 1H-->29Si CP/MAS NMR and 1H-29Si phase-modulated Lee-Goldburg decoupled correlation experiments demonstrate that the local environments of the silicon sites in the final hydrated sample are mainly composed of Q2 [(SiO)2Si(OH)O(-)Na+], Q3 [(SiO)3Si(OH) and (SiO)3SiO(-)Na+] and Q4 [Si(OSi)4] groups.

Journal Article↗
PubMed2004

Growth-inhibitory effect of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, on ovarian carcinoma cell lines not dependent on peroxisome proliferator-activated receptor-gamma expression.

OBJECTIVES: Despite the advent of new chemotherapeutic drugs in recent decades, epithelial ovarian carcinoma (EOC) remains the leading cause of death from gynecologic cancers, and new therapeutic targets and agents are urgently needed. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a novel synthetic triterpenoid with anti-tumor activity against a wide range of tumors in vitro and in vivo. CDDO is a ligand for the peroxisome proliferator-activated receptor-gamma (PPARgamma). The aim of the present study was to evaluate CDDO activity in EOC cell lines in vitro. METHODS: The expression of PPARgamma was examined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in eight EOC cell lines (2774, SKOV3, CAOV3, OVCAR3, NMP-1, HEY, 2008 and 2008.C13), and the growth inhibitory activity of CDDO was assessed using the MTT assay. RESULTS: PPARgamma RNA was expressed in all eight cell lines examined, but the expression varied widely among cell lines. In contrast, CDDO showed a similar degree of activity in different EOC cell lines independent of cisplatin sensitivity, with 50% inhibitory concentrations ranging from 1 to 4 microM. Experiments combining CDDO with cisplatin and paclitaxel indicated weak antagonism. The growth-inhibitory activity of CDDO was unaffected by PPARgamma antagonist T007. CONCLUSIONS: Although differences were observed in PPARgamma expression in EOC cell lines, CDDO had similar growth-inhibitory activity in all cell lines examined, indicating that the antitumor activity of CDDO in vitro is mediated by a mechanism independent of PPARgamma. The activity of CDDO in platinum-resistant cell lines is encouraging with respect to the potential clinical use of the drug.

Antineoplastic Agents↗
PubMed2004

Analysis of purified tubulin in high concentration of glutamate for application in high throughput screening for microtubule-stabilizing agents.

High-throughput screening (HTS) is a powerful approach for the discovery of potential and effective drugs from a number of candidates. The dynamics of tubulin assembly and disassembly in vitro are an important target for the screening of anti-tumor agents. However, previously described methods are not amenable for HTS. In this paper, we compared preparation methods of tubulin and suggest a combination method, i.e., one cycle of assembly and disassembly following ion-exchange chromatography using high concentrations of glutamate to increase the recovery of tubulin with high purity. The resultant highly purified microtubule-associated proteins-free tubulin in high glutamate solution was directly employed in tubulin polymerization assays. Our results indicate that the system is feasible and practicable as a model for HTS for microtubule-stabilizing agents.

Chromatography, DEAE-Cellulose↗
PubMed2004

Cloning and expression analysis in mature individuals of two chicken type-II GnRH (cGnRH-II) genes in common carp (Cyprinus carpio).

Gonadotropin-releasing hormone (GnRH) is a conservative neurodecapeptide family, which plays a crucial role in regulating the gonad development and in controlling the final sexual maturation in vertebrate. Two differing cGnRH-II cDNAs of common carp, namely cGnRH-II cDNA1 and cDNA2, were firstly cloned from the brain by rapid amplification of cDNA end (RACE) and reverse transcription- polymerase chain reaction (RT-PCR). The length of cGnRH-II cDNA1 and cDNA2 was 622 and 578 base pairs (bp), respectively. The cGnRH-II precursors encoded by two cDNAs consisted of 86 amino acids, including a signal peptide, cGnRH-II decapeptide and a GnRH-associated peptide (GAP) linked by a Gly-Lys-Arg proteolytic site. The results of intron trapping and Southern blot showed that two differing cGnRH-II genes in common carp genome were further identified, and that two genes might exist as a single copy. The multi-gene coding of common carp cGnRH-II gene offered novel evidence for gene duplication hypothesis. Using semi-quantitative RT-PCR, expression and relative expression levels of cGnRH-II genes were detected in five dissected brain regions, pituitary and gonad of common carp. With the exception of no mRNA2 in ovary, two cGnRH-II genes could be expressed in all the detected tissues. However, expression levels showed an apparent difference in different brain regions, pituitary and gonad. According to the expression characterization of cGnRH-II genes in brain areas, it was presumed that cGnRH-II might mainly work as the neurotransmitter and neuromodulator and also operate in the regulation for the GnRH releasing. Then, the expression of cGnRH-II genes in pituitary and gonad suggested that cGnRH-II might act as the autocrine or paracrine regulator.

Aging↗
PubMed2004

A high-throughput model for screening anti-tumor agents capable of promoting polymerization of tubulin in vitro.

AIM: To establish a high-throughput model for screening anti-tumor agents capable of promoting the polymerization of tubulin in vitro. METHODS: Tubulin was prepared in different purity for two screening steps. The first step was a high-throughput screening (HTS) for a set of 1500 samples using the GTP-containing tubulin and the end-reading method. The second step was performed on 119 hits from the first screening by a kinetic assay with GTP-lacking tubulin. RESULTS: The HTS for 1500 samples was accomplished in less than 3 h. From the screening, 108 samples were identified with >20 % promotion activity at 10 mg/L. Five of 108 were further confirmed by the kinetic assay using the purified tubulin subsequently. Three of the hit compounds were Epothilone A or its analogs, the other two compounds had new structures with a common pharmacophore for cytotoxic natural products that stabilize microtubules. In an MTT test, the five selected samples from the screening showed a minimal IC(50) at 0.28+/-0.06 nmol/L to Hela cells. CONCLUSION: The two-step screening method is a high-throughtput, cost-effective, and efficient approach to identify microtubule-stabilizing agents.

Antineoplastic Agents↗