Biomedical subjects

Xueli Liu

Publications and source records attributed to Xueli Liu.

14 recordsLinked to original sources

PubMed2006

Lipopolysaccharide induces CXCL2/macrophage inflammatory protein-2 gene expression in enterocytes via NF-kappaB activation: independence from endogenous TNF-alpha and platelet-activating factor.

CXCL2 (macrophage inflammatory protein-2 (MIP-2)), a critical chemokine for neutrophils, has been shown to be produced in the rat intestine in response to platelet-activating factor (PAF) and to mediate intestinal inflammation and injury. The intestinal epithelium, constantly exposed to bacterial products, is the first line of defence against micro-organisms. It has been reported that enterocytes produce proinflammatory mediators, including tumour necrosis factor (TNF) and PAF, and we showed that lipopolysaccharide (LPS) and TNF activate nuclear factor (NF)-kappaB in enterocytes. However, it remains elusive whether enterocytes release CXCL2 in response to LPS and TNF via a NF-kappaB-dependent pathway and whether this involves the endogenous production of TNF and PAF. In this study, we found that TNF and LPS markedly induced CXCL2 gene expression in IEC-6 cells, TNF within 30 min, peaking at 45 min, while LPS more slowly, peaking after 2 hr. TNF- and LPS- induced CXCL2 gene expression and protein release were completely blocked by pyrrolidine dithiocarbamate (PDTC) and helenalin, two potent NF-kappaB inhibitors. NEMO-binding domain peptide, a specific inhibitor of inhibitor protein kappaB kinase (IKK) activation, a major upstream kinase mediating NF-kappaB activation, significantly blocked CXCL2 gene expression and protein release induced by LPS. WEB2170 (PAF antagonist) and anti-TNF antibodies had no effect on LPS-induced CXCL2 expression. In conclusion, CXCL2 gene is expressed in enterocytes in response to both TNF and LPS. LPS-induced CXCL2 expression is dependent on NF-kappaB activation via the IKK pathway. The effect of LPS is independent of endogenous TNF and PAF.

Animals↗

PubMed2005

Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma.

BACKGROUND: The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC. METHODS: The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival. RESULTS: The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001). CONCLUSIONS: The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.

Adenocarcinoma, Clear Cell↗

PubMed2005

Synthesis, characterization and biological activity of triorganotin 2-phenyl-1,2,3-triazole-4-carboxylates.

The triorganotin 2-phenyl-1,2,3-triazole-4-carboxylates, 2-PhC2N3CO2SnR3 (R=C6H5, 1; c-C6H11, 2; C6H5C(CH3)2CH2, 3), have been prepared and characterized by means of elemental analysis, IR and NMR (1H, 13C and 119Sn) spectroscopy. The crystal structures of 1 and 3 have been determined. Compound 1 is polymeric in nature with a trigonal bipyramidal configuration, and compound 3 shows a tetrahedral geometry. Bioassay results have shown that these compounds have good antibacterial and antitumor activity. The activity against three human tumor cell lines (HeLa, CoLo205 and MCF-7) decreased in the order 1>2>3.

Anti-Bacterial Agents↗

PubMed2005

The symmetry of longevity.

We tested the hypothesis that relatively symmetrical flies live longer. Vein measurements on the left and right wings from the same individual were used to characterize bilateral symmetry in relationship to age-specific survival in defined cohorts. A longitudinal cohort study supported the hypothesis of a correlation between bilateral symmetry and longevity. For another type of experiment, wings were removed from females and males at approximately the beginning of adult life. Thus, there would be no effect of wings per se on adult survival. These wings were measured to characterize bilateral asymmetry, and the day of death of each dewinged individual was determined. Wing symmetry of females and males proved to be a statistically significant predictor of life span, especially for males.

Animals↗

PubMed2005

Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma.

PURPOSE: Approximately 30% of renal cell carcinomas (RCCs) present as metastatic disease. Molecular markers have the potential to characterize accurately the biological behavior of tumors and they may be useful for determining prognosis. MATERIALS AND METHODS: A custom tissue array was constructed using clear cell RCC from 150 patients with metastatic RCC who underwent nephrectomy prior to immunotherapy. The tissue array was stained for 8 molecular markers, namely Ki67, p53, gelsolin, carbonic anhydrase (CA)9, CA12, PTEN (phosphatase and tensin homologue deleted on chromosome 10), epithelial cell adhesion molecule and vimentin. Marker status and established clinical predictors of prognosis were considered when developing a prognostic model for disease specific survival. RESULTS: On univariate Cox regression analysis certain markers were statistically significant predictors of survival, namely CA9 (p <0.00001), p53 (p = 0.0072), gelsolin (p = 0.030), Ki67 (p = 0.036) and CA12 (p = 0.043). On multivariate Cox regression analysis that included all markers and clinical variables CA9 (p = 0.00002), PTEN (p <0.0001), vimentin (p = 0.0032), p53 (p = 0.028), T category (p = 0.0025) and performance status (p = 0.0013) were significant independent predictors of disease specific survival and they were used to construct a combined molecular and clinical prognostic model. The bias corrected concordance index (C-index) of this combined prognostic model was C = 0.68, which was significantly higher (p = 0.0033) than that of a multivariate clinical predictor model (C = 0.62) based on the UCLA Integrated Staging System (T category, histological grade and performance status). CONCLUSIONS: In patients with clear cell RCC a prognostic model for survival that includes molecular and clinical predictors is significantly more accurate than a standard clinical model using the combination of stage, histological grade and performance status.

Adult↗

PubMed2005

Expression of transcription factor Yin Yang 1 in prostate cancer.

The transcription repressor Yin Yang 1 (YY1) is expressed in several human cancer cell lines and its expression correlates with resistance to immune-mediated apoptosis. This study used tissue microarrays to investigate the expression and localization of YY1 in 1364 representative tissue samples from 246 hormone naive prostate cancer patients who underwent radical prostatectomy. Staining intensity and frequency measures for both YY1 nuclear and cytoplasmic expression were higher in neoplastic tissues and in PIN samples compared to matched benign cells (p < 0.0001 for all comparisons). Expression of YY1 is predominantly elevated in early malignancy (PIN), as well as in tumors of intermediate to high morphologic grade (Gleason's grade 3-5). Using multivariate Cox proportional hazards analysis, we observed that low nuclear YY1 staining is an independent predictor of a shorter time to recurrence (p = 0.012). Based on these results, we hypothesize that YY1 may play a role in prostate cancer development; however, decreased YY1 may give metastatic cells a survival advantage. These results may also implicate YY1 as a useful diagnostic and prognostic marker.

Aged↗

PubMed2005

Thymic nurse cells support CD4-CD8+ thymocytes to differentiate into CD4+CD8+ cells.

Thymic nurse cells (TNCs) represent a unique microenvironment in the thymus for T cell maturation. In order to investigate the role of thymic nurse cells during T cell differentiation, a TNC clone, RWTE-1, which formed a typical complex with fetal thymocytes in vitro was established from normal Wistar rat. Hanging drop culture method was applied to reveal the interaction between TNCs and thymocytes. Our result revealed that eighty percent of immature CD4(-)CD8(+) cells differentiated into CD4(+)CD8(+) cells after a 12-hour hanging drop culture with RWTE-1. However, in a 12-hour culture of immature CD4(-)CD8(+) cells with or without RWTE-1 supernatant, only 30% of the cells differentiated into CD4(+)CD8(+) cells spontaneously. This observation led to the conclusion that RWTE-1 cell has the capacity to facilitate immature CD4(-)CD8(+) thymocytes to differentiate into CD4(+)CD8(+) T cells by direct interaction.

Animals↗

PubMed2004

Macrophage inflammatory protein-2 mediates the bowel injury induced by platelet-activating factor.

Platelet-activating factor (PAF) is a potent endogenous mediator of bowel inflammation. It activates neutrophils that are needed to initiate the inflammatory response. Macrophage inflammatory protein-2 (MIP-2), a critical C-X-C chemokine secreted by macrophages and epithelial cells, is a potent chemoattractant for neutrophils. Whereas MIP-2 has been previously shown to mediate the injury in various organs, its role in acute intestinal injury has never been assessed. In this study, we first investigated the effect of PAF on MIP-2 expression in the intestine. Anesthetized young adult male Sprague-Dawley rats were injected intravenously with either PAF (1.5 microg/kg) or saline. Sixty minutes later, ileal MIP-2 gene expression was determined by semiquantitative RT-PCR, and plasma and ileal MIP-2 protein was determined by ELISA. In a second step, we assessed the role of MIP-2 in PAF-induced bowel injury. Rats were pretreated with rabbit anti-rat MIP-2 antibodies or control IgG for 90 min and then injected intravenously with PAF (2.5 microg/kg) for 90 min. We found that, in the rat intestine, 1) MIP-2 mRNA was only minimally expressed constitutively in sham-operated animals; 2) MIP-2 mRNA was significantly upregulated in response to PAF; 3) MIP-2 protein plasma levels and local production of MIP-2 in the ileum were markedly induced by PAF; 4) the administration of anti-rat MIP-2 IgG, but not control rabbit IgG, markedly reduced PAF-induced bowel injury (injury scores of 0.19 +/- 0.09 vs. 1.12 +/- 0.43, P < 0.05), hypotension, and leukopenia but did not reduce PAF-induced hemoconcentration. Thus we conclude that MIP-2 mediates PAF-induced intestinal injury.

Animals↗

PubMed2004

Using protein expressions to predict survival in clear cell renal carcinoma.

PURPOSE: An accurate system for predicting survival for patients with solid tumors will allow for better patient selection for both established and novel therapies. We propose a staging system for clear cell variants of renal cell carcinoma (RCC) that includes molecular predictors and standard clinical predictors such as tumor-node-metastasis (TNM) stage, histological grade, and performance status (PS). EXPERIMENTAL DESIGN: A custom tissue array was constructed using clear cell RCC from 318 patients, representing all stages of localized and metastatic RCC, and immunohistochemically stained for molecular markers Ki67, p53, gelsolin, CA9, CA12, PTEN, EpCAM, and vimentin. We present a strategy for evaluating individual candidate markers for prognostic information and integrating informative markers into a multivariate prognostic system. RESULTS: The overall median follow-up and the median follow-up for surviving patients were 28 and 55 months, respectively. A prognostic model based primarily on molecular markers included metastasis status, p53, CA9, gelsolin, and vimentin as predictors and had high discriminatory power: its statistically validated concordance index (C-index) was found to be 0.75. A prognostic model based on a combination of clinical and molecular predictors included metastasis status, T stage, Eastern Cooperative Oncology Group PS, p53, CA9, and vimentin as predictors and had a C-index of 0.79, which was significantly higher (P < 0.05) than that of prognostic models based on grade alone (C = 0.65), TNM stage alone (C = 0.73), or the University of California Los Angeles integrated staging system (C = 0.76). CONCLUSIONS: Protein expressions obtained using widely available technology can complement standard clinical predictors such as TNM stage, histological grade, and PS.

Adenocarcinoma, Clear Cell↗

PubMed2004

Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies. EXPERIMENTAL DESIGN: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92). CONCLUSIONS: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.

Adenocarcinoma, Clear Cell↗

PubMed2004

Statistical methods for analyzing tissue microarray data.

Tissue microarrays (TMAs) are a new high-throughput tool for the study of protein expression patterns in tissues and are increasingly used to evaluate the diagnostic and prognostic importance of biomarkers. TMA data are rather challenging to analyze. Covariates are highly skewed, non-normal, and may be highly correlated. We present statistical methods for relating TMA data to censored time-to-event data. We review methods for evaluating the predictive power of Cox regression models and show how to test whether biomarker data contain predictive information above and beyond standard pathology covariates. We use nonparametric bootstrap methods to validate model fitting indices such as the concordance index. We also present data mining methods for characterizing high risk patients with simple biomarker rules. Since researchers in the TMA community routinely dichotomize biomarker expression values, survival trees are a natural choice. We also use bump hunting (patient rule induction method), which we adapt to the use with survival data. The proposed methods are applied to a kidney cancer tissue microarray data set.

Algorithms↗

PubMed2004

Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsular invasion in prostate cancer.

PURPOSE: Few successful therapeutic options exist for men who present with metastatic prostate cancer (CaP) or for the 30% with recurrence. The development and characterization of molecular markers are vital to the development of prognostic and therapeutic modalities in CaP. We investigated the expression and potential clinical usefulness of prostate stem cell antigen (PSCA) in CaP using tissue microarrays. MATERIALS AND METHODS: Immunohistochemical analysis using a PSCA monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 246 patients who underwent radical retropubic prostatectomy. PSCA staining was correlated with established prognostic factors, such as Gleason score, prostate specific antigen (PSA), and seminal vesicle invasion. In addition, recurrence-free survival was analyzed. RESULTS: A high PSCA intensity of 3 was associated with adverse prognostic features, such as Gleason score 7 and above (p = 0.001), seminal vesicle invasion (p = 0.005) and capsular involvement (p = 0.033). On univariate analysis tumors with a PSCA intensity of 3 carried an increased risk of PSA recurrence (p = 0.031, HR 1.77, 95% CI 1.05 to 2.96). However, after adjusting for these variables a PSCA intensity of 3 was no longer an independent predictor of PSA recurrence. CONCLUSIONS: We found that high PSCA intensity is significantly associated with adverse prognostic features such as high Gleason score and extra-organ disease. The results of this study suggest that PSCA is a promising tumor marker for the selection of patients at high risk but additional studies are necessary to assess the usefulness of PSCA in patient biopsies.

Aged↗

PubMed2003

Modes and clustering for time-warped gene expression profile data.

MOTIVATION: The study of the dynamics of regulatory processes has led to increased interest for the analysis of temporal gene expression level data. To address the dynamics of regulation, expression data are collected repeatedly over time. It is difficult to statistically represent the resulting high-dimensional data. When regulatory processes determine gene expression, time-warping is likely to be present, i.e. the sample of gene expression trajectories reflects variation not only in terms of the expression amplitudes, but also in terms of the temporal structure of gene expression. RESULTS: A non-parametric time-synchronized iterative mean updating technique is proposed to find an overall representation that corresponds to a mode of a sample of expression profiles, viewed as a random sample in function space. The proposed algorithm explores the application of previous work of Hall and Heckman to genome-wide expression data and provides an extension that includes random time-warping with the aim to synchronize timescales across genes. The proposed algorithm is universally applicable for the construction of modes for functional data with time-warping. We demonstrate the construction of mode functions for a sample of Drosophila gene expression data. The algorithm can be applied to define clusters among the observed trajectories of gene expression, without any kind of prior non-time-warped clustering, as illustrated in the numerical example.

Adaptation, Physiological↗

PubMed2002

Supine behaviour predicts the time to death in male Mediterranean fruitflies (Ceratitis capitata).

Over 97% of the 203 male medflies monitored in a lifetime study of their behaviour exhibited what we term supine behaviour (temporary upside-down orientation) starting an average of 16.1 days prior to their death (mean lifespan of 61.7 days). Supine onset increased the mortality risk by 39.5-fold and a unit increase in supine level increased mortality by 26.3%. The discovery that behavioural traits in insects can be used as biomarkers of their health and to predict their time to death has important implications regarding research on morbidity dynamics, behavioural neuroethology and gerontology, and the interpretation of longevity extension in model organisms.

Aging↗