Biomedical subjects

Ziding Feng

Publications and source records attributed to Ziding Feng.

At least 19 recordsLinked to original sources

PubMed2024

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified Delphi panel.

HCC surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on 21 statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities. The experts agreed that current data have methodologic limitations as well as unclear generalizability to Western populations. Although a randomized clinical trial of surveillance versus no surveillance is unlikely feasible, they concurred that alternative designs, such as a comparison of 2 surveillance modalities, could provide indirect evidence of surveillance efficacy. The panel acknowledged the presence of surveillance harms, but concurred the overall value of surveillance appears high, particularly given a greater emphasis on benefits over harms by both patients and clinicians. The experts underscored the importance of a framework for measuring both benefits and harms when evaluating emerging surveillance strategies. The panel acknowledged performance metrics of emerging methods may differ from other cancer screening programs given differences in populations, including higher risk of cancer development and competing risk of morality, and differences in diagnostic workflow in patients at risk of HCC. These data provide insights into the perceived value of HCC surveillance in an era of emerging blood- and imaging-based surveillance strategies.

Humans↗

PubMed2006

Polymorphisms in the glutathione S-transferase M1, T1, and P1 genes and prostate cancer prognosis.

BACKGROUND: Polymorphisms in glutathione S-transferase (GST) genes can increase oxidative stress, which may affect cancer prognosis. The aim of this study was to examine associations between GSTM1, T1, or P1 genetic variants and prostate cancer outcomes. METHODS: A population-based cohort of men (n = 752) from King County, Washington, diagnosed with prostate cancer in 1993-1996, and under long-term surveillance for mortality completed a follow-up survey about prostate cancer recurrence/progression. Cox PH models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for deaths from prostate cancer or other causes and prostate cancer recurrence/progression. RESULTS: There were 50 prostate cancer-specific deaths, 65 deaths from other causes, and 143 recurrence/progressions events during an average 9.6 years of follow-up. The adjusted HR for prostate cancer mortality was 3.8 (95% CI 1.6-8.9) among Caucasian men with the GSTM1-null genotype. There were no differences, however, in mortality from other causes or prostate cancer recurrence/progression between men with GSTM1-null versus not-null genotypes. The GSTT1 and GSTP1 genotypes were not associated with any of these outcomes. DISCUSSION: Results suggest that the GSTM1 genotype may be a useful biomarker to identify patients at higher risk for fatal prostate cancer.

Biomarkers, Tumor↗

PubMed2006

Reproducible two-dimensional capillary electrophoresis analysis of Barrett's esophagus tissues.

We have constructed a high-speed, two-dimensional capillary electrophoresis system with a compact and high-sensitivity fluorescence detector. This instrument is used for the rapid and reproducible separations of Barrett's esophagus tissue homogenates. Proteins and biogenic amines are labeled with the fluorogenic reagent 3-(2-furoyl)quinoline-2-carboxaldehyde. Labeled biomolecules are separated sequentially in two capillaries. The first capillary employs capillary sieving electrophoresis using a replaceable sieving matrix. Fractions are successively transferred to a second capillary where they undergo additional separation by micellar electrokinetic capillary chromatography. The comprehensive two-dimensional separation requires 60 min. Within-day migration time reproducibility is better than 1% in both dimensions for the 50 most intense features. Between-day migration time precision is 1.3% for CSE and better than 0.6% for MECC. Biopsies were obtained from the squamous epithelium in the proximal tubular esophagus, Barrett's epithelium from the distal esophagus, and fundus region of the stomach from each of three Barrett's esophagus patients with informed consent. We identified 18 features from the homogenate profiles as biogenic amines and amino acids. For each of the patients, Barrett's biopsies had more than 5 times the levels of phenylalanine and alanine as compared to squamous tissues. The patient with high-grade dysplasia shows the highest concentrations for 13 of the amino acids across all tissue types. Concentrations of glycine are 40 times higher in squamous biopsies compared to Barrett's and fundal biopsies from the patient with high-grade dysplasia. These results suggest that two-dimensional capillary electrophoresis may be of value for the rapid characterization of endoscopic and surgical biopsies.

Amines↗

PubMed2006

Ultrasensitive detection and characterization of posttranslational modifications using surface-enhanced Raman spectroscopy.

Posttranslational modification (PTM) of proteins is likely to be the most common mechanism of altering the expression of genetic information. It is essential to characterize PTMs to establish a complete understanding of the activities of proteins. Here, we present a sensitive detection method using surface-enhanced Raman spectroscopy (SERS) that can detect PTMs from as little as zeptomoles of peptide. We demonstrate, using model peptides, the ability of SERS to detect a variety of protein modifications, such as acetylation, trimethylation, phosphorylation, and ubiquitination. In addition, we show the capability to obtain positional information for modifications such as trimethylation and phosphorylation using SERS and wavelet decomposition data analysis techniques. We further show that it is possible to apply SERS to detect PTMs from biological samples such as histones. We envision that this detection method might be a valuable technique that is complementary to mass spectrometry in obtaining orthogonal chemical and modification-specific information from biological samples at sensitive levels.

Acetylation↗

PubMed2006

Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and the risk of fibrocystic breast conditions among Chinese women.

We investigated whether circulating insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case-control study nested within a randomized trial of breast self-examination conducted in Shanghai, China. Participants were enrolled during 1989-1991 and were followed over 10 years for the development of breast diseases. Controls (n = 897) were frequency-matched by age to cases (n = 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF-I and IGFBP-3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF-I, IGFBP3 and their molar ratio were 3.02 (2.02-4.52), 1.92 (1.37-2.71) and 2.26 (1.52-3.36), respectively. The strength of the association between IGF-I levels and FBC was attenuated after adjustment for IGFBP-3 and that for IGFBP-3 was largely eliminated after adjustment for IGF-I. Increasing levels of IGF-I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF-I: 3.13 (1.50-6.53), 4.57 (2.22-9.39) and 6.30 (3.08-12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF-I may contribute to the development of FBC.

Adult↗

PubMed2006

Application of a methylation gene panel by quantitative PCR for lung cancers.

Detection of lung cancer at early stages could potentially increase survival rates. One promising approach is the application of suitable lung cancer-specific biomarkers to specimens obtained by non-invasive methods. Thus far, clinically useful biomarkers that have high sensitivity have proven elusive. Certain genes, which are involved in cellular pathways such as signal transduction, apoptosis, cell to cell communication, cell cycles and cytokine signaling are down-regulated in cancers and may be considered as potential tumor suppressor genes. Aberrant promoter hypermethylation is a major mechanism for silencing tumor suppressor genes in many kinds of human cancers. Using quantitative real time PCR, we tested 11 genes (3-OST-2, RASSF1A, DcR1, DcR2, P16, DAPK, APC, ECAD, HCAD, SOCS1, SOCS3) for levels of methylation within their promoter sequences in non-small cell lung cancers (NSCLC), adjacent non-malignant lung tissues, in peripheral blood mononuclear cells (PBMC) from cancer free patients, in sputum of cancer patients and controls. Of all the 11 genes tested 3-OST-2 showed the highest levels of promoter methylation in tumors combined with lowest levels of promoter methylation in control tissues. 3-OST-2 followed by, RASSF1A showed increased levels of methylation with advanced tumor stage (P<0.05). Thus, quantitative analysis of 3-OST-2 and RASSF1A methylation appears to be a promising biomarker assay for NSCLC and should be further explored in a clinical study. Our preliminary data on the analysis of sputum DNA specimens from cancer patients further support these observations.

Adenocarcinoma↗

PubMed2006

Modeling, estimation and validation of cotton dust and endotoxin exposures in Chinese textile operations.

In support of an epidemiological study of cancer incidence among cotton textile workers in Shanghai, PRC, historical estimates of exposure to cotton dust and endotoxin were developed for subjects drawn from a cohort of 267,400 female textile workers. A large dataset of historical cotton dust measurements were available from 56 of the study factories. Using these data, a series of models were developed to estimate cotton dust exposure by year, factory and process. Model estimates were validated by comparing with independently collected measurements gathered over a 15 year period and indicated a low relative bias (< 2%) and relative accuracy (+/- 61%). Endotoxin exposures were estimated using the endotoxin content of cotton dust by major processes obtained in five separate surveys in these factories. The validated exposures were assigned to the 7,242 jobs held by the 3,812 study subjects. Among the exposed workers, the mean cumulative exposure levels were 113.8 mg m(-3)*years for cotton dust and 6,707.7 EU m(-3)*years for endotoxin, respectively. The overall correlation among cotton dust and endotoxin exposures for these subjects was r = 0.58. Using an unusually rich set of historical cotton dust measurements, along with independently collected exposure measurements for validation and conversion to endotoxin levels, validated estimates of cumulative exposure were constructed for this large case-cohort study in the textile industry.

China↗

PubMed2006

Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial.

BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who participated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. METHODS: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. RESULTS: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score > or =7) whereas a previous negative prostate biopsy reduced this risk. CONCLUSIONS: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy.

Black or African American↗

PubMed2006

Sun exposure related methylation in malignant and non-malignant skin lesions.

We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P<0.0001). While weak signals were detected in the SP samples by real time PCR, the differences between SE and SP specimens were 148 fold for tags and 390 fold for BCCs. These differences were highly significant (P<0.0001). These findings suggest that methylation commences in UV exposed skin at a relatively early age and occurs in skin prior to the onset of recognizable preneoplastic changes.

Aged↗

PubMed2006

Aberrant promoter methylation of multiple genes during multistep pathogenesis of colorectal cancers.

Aberrant methylation of 5'gene promoter regions associated with gene silencing is an epigenetic phenomenon responsible for silencing of tumor suppressor genes in many cancer types. The aims of our study were to study the role of methylation of a large panel of genes during multistage pathogenesis and to correlate our findings with patient age and other clinico-pathological features. We investigated the aberrant promoter methylation profile of 19 genes in 92 colorectal cancers (CRCs) and corresponding nonmalignant epithelia (NME) (n = 57), and selected 15 genes for studying 26 colorectal adenomas (CAs). On the Basis of our results, the genes could be divided into 3 groups. Group 1 consisted of 13 genes whose methylation was tumor-specific. For 8 of these genes, the methylation frequencies in CAs were similar to those of CRCs, but significantly different from the frequencies in NME. Group 2, consisting of 2 genes demonstrating little or no methylation, were present in any sample type. In Group 3, consisting of 4 genes, relatively frequent methylation was present in both CRCs and NME, and the differences between these specimen types were not significant. Methylation of Group 1 genes were tightly correlated with each other, and these genes demonstrated increased methylation frequencies in CRCs with increasing age. Methylation was not correlated with other clinico-pathological features. In general, methylation frequencies of CAs were intermediate between CRCs and NME. Our study constitutes the most comprehensive methylation profile of CRCs, demonstrates that methylation commences early during CRC pathogenesis and is an age-related phenomenon.

Aged↗

PubMed2006

Occupational risk factors for esophageal and stomach cancers among female textile workers in Shanghai, China.

The authors evaluated associations between occupational exposures in the textile industry and the risks of esophageal cancer and stomach cancer. The authors conducted a case-cohort study nested in a cohort of female textile workers in Shanghai, China. One hundred and two workers with incident esophageal cancer and 646 workers with incident stomach cancer diagnosed between 1989 and 1998 were compared with an age-stratified reference subcohort (n = 3,188). Work histories were ascertained for all study subjects from factory personnel records or interviews. Exposures were reconstructed for chemicals and dusts by linking work history data with a job-exposure matrix developed for the Shanghai textile industry. Hazard ratios and 95 percent confidence intervals were calculated with Cox proportional hazards modeling adapted for the case-cohort design. Risk of esophageal cancer was associated with long-term (> or = 10 years) exposure to silica dust (hazard ratio = 15.8, 95% confidence interval: 3.5, 70.6) and metals (hazard ratio = 3.7, 95% confidence interval: 1.9, 7.1). Cumulative exposure to endotoxin, a contaminant of cotton dust, was inversely related to risks of both esophageal cancer (p-trend = 0.01) and stomach cancer (p-trend < 0.001) when exposures were lagged 20 years. Endotoxin has not been previously reported to be a protective factor for either stomach cancer or esophageal cancer and therefore warrants further study.

Aged↗

PubMed2006

A controlled, household-randomized, open-label trial of the effect that treatment of Helicobacter pylori infection has on iron deficiency in children in rural Alaska.

BACKGROUND: Helicobacter pylori infection and iron deficiency are prevalent in disadvantaged populations worldwide. Previous small or uncontrolled studies have reported that successful treatment of H. pylori infection may resolve iron deficiency or anemia. METHODS: We screened 68% of children 7-11 years old living in 10 western Alaska villages. The 219 children with iron deficiency (serum ferritin level, <22.5 pmol/L [<10 microg/L]) and H. pylori infection (diagnosed on the basis of (13)C-labeled urea breath tests) were enrolled in a household-randomized, unblinded trial. All children received iron supplementation for 6 weeks; children in the intervention group also received a 2-week course of treatment for H. pylori infection plus another 2-week course of treatment if the infection had not resolved at 2 months after treatment initiation. RESULTS: At 2 months after treatment initiation, 32% of children in the intervention group and 39% of children in the control group had iron deficiency. At 14 months after treatment initiation, 65% of children in the intervention group and 72% of children in the control group had iron deficiency (adjusted relative risk [ARR], 0.90 [95% confidence interval [CI], 0.74-1.1]); in addition, 22% of children in the intervention group and 14% of children in the control group had anemia (ARR, 1.6 [95% CI, 0.86-2.9]). Results were similar when children were compared by H. pylori infection status. CONCLUSIONS: In a high-prevalence population, treatment and resolution of H. pylori infection did not improve isolated iron deficiency or mild anemia up to 14 months after treatment initiation.

Alaska↗

PubMed2006

Application of the time-dependent ROC curves for prognostic accuracy with multiple biomarkers.

The rapid advancement in molecule technology has led to the discovery of many markers that have potential applications in disease diagnosis and prognosis. In a prospective cohort study, information on a panel of biomarkers as well as the disease status for a patient are routinely collected over time. Such information is useful to predict patients' prognosis and select patients for targeted therapy. In this article, we develop procedures for constructing a composite test with optimal discrimination power when there are multiple markers available to assist in prediction and characterize the accuracy of the resulting test by extending the time-dependent receiver operating characteristic (ROC) curve methodology. We employ a modified logistic regression model to derive optimal linear composite scores such that their corresponding ROC curves are maximized at every false positive rate. We provide theoretical justification for using such a model for prognostic accuracy. The proposed method allows for time-varying marker effects and accommodates censored failure time outcome. When the effects of markers are approximately constant over time, we propose a more efficient estimating procedure under such models. We conduct numerical studies to evaluate the performance of the proposed procedures. Our results indicate the proposed methods are both flexible and efficient. We contrast these methods with an application concerning the prognostic accuracies of expression levels of six genes.

Biomarkers↗

PubMed2006

Telomere length in the colon declines with age: a relation to colorectal cancer?

Telomeres shorten with age, which may be linked to genomic instability and an increased risk of cancer. To explore this association, we analyzed telomere length in normal colorectal tissue of individuals at different ages using quantitative-fluorescence in situ hybridization (Q-FISH) and quantitative-PCR (Q-PCR). Using Q-FISH, we also examined the histologically normal epithelium adjacent to, or distant from, colon adenomas and cancers, in addition to the neoplasms. Q-FISH and Q-PCR showed that telomere length was inversely associated with age until approximately ages 60 to 70; surprisingly, beyond this age, telomere length was positively associated with age. This association was found exclusively in epithelial, and not in stromal, cells. Peripheral blood lymphocytes showed an inverse association between telomere length and age, but without any apparent increase in telomere length in the oldest individuals. Telomere length in larger adenoma lesions (>2 cm) was significantly shorter than in normal adjacent (P = 0.004) or normal distant (P = 0.05) tissue from the same individuals. However, telomere length in histologically normal epithelium adjacent to cancers or in adenomas <2 cm was not statistically different from that of the normal distant mucosa or from normal controls, evidence that a telomere-shortening field effect was not present. We suggest that the positive association between telomere length and age in the oldest patients is a consequence of selective survival of elderly patients with long colonocyte telomeres.

Adolescent↗

PubMed2006

Brain tumors and occupational exposures in a cohort of female textile workers in Shanghai, China.

OBJECTIVES: This study assessed the associations between brain tumors and specific processes and exposures among female textile workers in Shanghai, China. METHODS: A case-cohort study was conducted that was nested in a cohort of textile workers originally included in a randomized trial of breast self-examination. Incident brain tumor cases (N=114) were identified from 1989 to 1998 from a tumor and death registry operated by the Shanghai Textile Industry Bureau. A subcohort (N=3188), representing an age-stratified random sample of the entire cohort, was selected as a comparison group. Job-exposure matrices were created to assess historical exposures to specific agents, including quantitative assessments for cotton dust and endotoxin exposure. Cox proportional hazards modeling, modified according to a case-cohort design, was used to analyze associations between jobs and exposures and the risk of brain tumors. RESULTS: Employment in maintenance workshops was associated with an increased brain tumor incidence (ever-never exposed hazard ratio 2.36, 95% confidence interval 1.12-4.97), with increasing hazard ratios by duration of employment in maintenance jobs. Handling or processing wool fibers was associated with an increased risk of brain tumors, as was specific exposure to wool fibers; however, estimates did not increase with duration of employment. CONCLUSIONS: These results provide some preliminary suggestion that employment in textile industry maintenance jobs and exposure to wool products may be associated with an increased risk of brain tumors.

Aged↗

PubMed2005

A new family-based association test via a least-squares method.

To test the association between a dichotomous phenotype and genetic marker based on family data, we propose a least-squares method using the vector of phenotypes and their cross products within each family. This new approach allows covariate adjustment and is numerically much simpler to implement compared to likelihood- based methods. The new approach is asymptotically equivalent to the generalized estimating equation approach with a diagonal working covariance matrix, thus avoiding some difficulties with the working covariance matrix reported previously in the literature. When applied to the data from Collaborative Study on the Genetics of Alcoholism, this new method shows a significant association between the marker rs1037475 and alcoholism.

Family↗

PubMed2005

Antibody microarray profiling reveals individual and combined serum proteins associated with pancreatic cancer.

We used antibody microarrays to probe the associations of multiple serum proteins with pancreatic cancer and to explore the use of combined measurements for sample classification. Serum samples from pancreatic cancer patients (n = 61), patients with benign pancreatic disease (n = 31), and healthy control subjects (n = 50) were probed in replicate experiment sets by two-color, rolling circle amplification on microarrays containing 92 antibodies and control proteins. The antibodies that had reproducibly different binding levels between the patient classes revealed different types of alterations, reflecting inflammation (high C-reactive protein, alpha-1-antitrypsin, and serum amyloid A), immune response (high IgA), leakage of cell breakdown products (low plasma gelsolin), and possibly altered vitamin K usage or glucose regulation (high protein-induced vitamin K antagonist-II). The accuracy of the most significant antibody microarray measurements was confirmed through immunoblot and antigen dilution experiments. A logistic-regression algorithm distinguished the cancer samples from the healthy control samples with a 90% and 93% sensitivity and a 90% and 94% specificity in duplicate experiment sets. The cancer samples were distinguished from the benign disease samples with a 95% and 92% sensitivity and an 88% and 74% specificity in duplicate experiment sets. The classification accuracies were significantly improved over those achieved using individual antibodies. This study furthered the development of antibody microarrays for molecular profiling, provided insights into the nature of serum-protein alterations in pancreatic cancer patients, and showed the potential of combined measurements to improve sample classification accuracy.

Adenocarcinoma↗

PubMed2005

Quantifying peptide signal in MALDI-TOF mass spectrometry data.

This study addressed the question of which properties in MALDI-TOF spectra are relevant to the task of identifying mass and abundance of a peptide species in human serum. Data of this type are common to biomarker studies, but significant within- and between-spectrum variabilities make quantifying biologically induced features difficult. We investigated this signal content and quantified the existence, or lack, of peptide-induced signal (as manifest in a multiresolution decomposition) by generating spectra from human serum in which the abundance of peptides of specific masses is controlled by a sequence of dilutions. The intensities of the corresponding features were directly proportional to peptide concentration. The primary goal was to exhibit some quantifiable properties of raw spectra from this application of MALDI-TOF mass spectrometry. Although no recommendations are given regarding the best method for processing these data, the results confirm the utility of a simple method, based on wavelets, for defining and quantifying features related to low abundance peptide species in a heterogeneous set of complex spectra. Estimates on lower limits of detectable peptide abundance (in the 20-nmol range) and on the number of features present in a spectrum are made possible by the controlled experimental design, the use of a large external reference data set, and dependence on relatively few modeling assumptions.

Animals↗