Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biomarker development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed2002

Comparison of inhibition of ovalbumin-induced bronchoconstriction in guinea pigs and in vitro inhibition of tumor necrosis factor-alpha formation with phosphodiesterase 4 (PDE4) selective inhibitors.

Phosphodiesterase 4 (PDE4) inhibitors elevate cyclic adenosine 5'-monophosphate (cAMP), and this elevation has been shown to inhibit inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). Using TNF-alpha as a biomarker, we have developed transcription-based assays to examine inhibition of PDE4 activity in human and guinea pig whole blood. In vitro inhibition by PDE4 inhibitors was measured using quantitative PCR (qPCR) analysis of TNF-alpha mRNA levels in whole blood stimulated with lipopolysaccharide (LPS). The kinetics of human TNF-alpha mRNA production were analyzed and shown to be highest 4 hr following LPS stimulation. The guinea pig displayed kinetics of TNF-alpha transcription similar to those of the human. Analysis of inhibition of human TNF-alpha protein production was performed by immunoassay and shown to correlate with inhibition of transcription for three of the four compounds tested. Roflumilast was found to be 9-fold more potent for TNF-alpha inhibition in the qPCR assay than in the protein assay. The potencies of L-826,141 and roflumilast were determined in human and guinea pig whole blood by qPCR, with IC(50) values of 270 and 20 nM, respectively, in humans and 100 and 10 nM, respectively, in guinea pigs. These results show that the potency of PDE4 inhibitors can be monitored in whole blood using a transcription-based assay, and that this type of assay can be adapted to various species provided the TNF-alpha nucleotide sequence is known. The in vitro whole blood IC(50) for TNF-alpha inhibition was compared to inhibition in the ovalbumin-challenged guinea pig model of bronchoconstriction. Obtaining plasma levels at the IC(50) determined in vitro for L-826,141 and roflumilast provides significant inhibition of bronchoconstriction. This suggests that TNF-alpha can be used as a whole blood biomarker in the guinea pig for PDE4 inhibition in this inflammatory model.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Clinical models of chemoprevention for colon cancer.

Colon cancer is a common malignancy in the westernized world and is incurable in its advanced stages. This article summarizes the currently available information on colorectal cancer chemoprevention. A brief outline of the incidence and etiologic factors is followed by a discussion of the evidence on which chemopreventive strategies for colon cancer are modeled. This includes a description of the development of surrogate endpoint biomarkers and experimental models to study colorectal cancer chemopreventives, a review of the promising colorectal cancer chemopreventives, and a discussion of the issues to be addressed in the design of future chemoprevention trials. The article concludes with an emphasis on the development and validation of biomarkers and selection of high-risk cohorts using genetic and epidemiologic tools as the main goals of future colon cancer chemoprevention trials before large-scale, risk-reduction trials are conducted.

Animals↗
PubMed1991

Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa. A multivariate analysis.

A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high-risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid beta-galactosidase (EC 3.2.1.23), sulpho- and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high-risk group, the carcinoma carriers having intermediate values between average-risk and high-risk patients. In a two-group discriminant analysis, high-risk or carcinoma patients could be separated from average-risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high-risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal-appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies.

Aged↗
PubMed2006

Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. EXPERIMENTAL DESIGN: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. RESULTS: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. CONCLUSIONS: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.

Biomarkers, Tumor↗
PubMed2006

Metallothionein-1 and -2 expression in cadmium- or arsenic-derived human malignant urothelial cells and tumor heterotransplants and as a prognostic indicator in human bladder cancer.

The goal of this study was to determine if the expression of the metallothionein (MT)-1/2 proteins might serve as a biomarker for the development of bladder cancer. A retrospective analysis of MT-1/2 staining was performed on 343 tissue sections from patients referred for the diagnosis of bladder cancer. The specimens were subdivided into six categories: benign, dysplastic, low-grade cancer, high-grade cancer with no evidence of invasion, high-grade cancer with evidence of invasion, and carcinoma in situ. There was no expression of MT-1/2 in benign lesions and low-grade cancers, a low incidence of expression in dysplastic lesions and high-grade cancers with no evidence of muscle invasion, and a significantly increased incidence of MT-1/2 in high-grade cancers that had invaded the underlying matrix. The expression of MT-1/2 varied in intensity from sample to sample and was focal in its expression. It was concluded from these findings that MT-1/2 may be a prognostic marker for cancers that are progressing to invade the underlying stroma of the bladder wall. The expression of MT-1/2 was also determined in a cell culture model of human urothelium that had been malignantly transformed by Cd2+ and As3+ and shown to be capable of tumor formation in nude mice. It was demonstrated that the expression of MT-1/2 in the tumor heterotransplants was similar to the pattern found in archival specimens of high-grade bladder cancers. The MT-1/2 staining in the heterotransplants was focal in pattern, varied in intensity, and highest in the less differentiated cells of the tumor. These findings indicate that the cell culture model may serve to help define the role of MT-1/2 expression in bladder cancer invasion.

Animals↗
PubMed2025

Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals. By comparing MN methylation with an atlas of tissue methylation we have derived a MN-specific signature of hypomethylated genomic regions, which accords with genes important for MN function. Through simulation we have optimised the selection of regions for biomarker detection in plasma and CSF cell-free DNA (cfDNA). However, we show that MN-derived DNA is not detectable via WGBS in plasma cfDNA. In support of our experimental finding, we show theoretically that the relative sparsity of lower MN sets a limit on the proportion of plasma cfDNA derived from MN which is below the threshold for detection via WGBS. Our findings are important for the ongoing development of ALS biomarkers. The MN-specific hypomethylated genomic regions we have derived could be usefully combined with more sensitive detection methods and perhaps with study of CSF instead of plasma. Indeed we demonstrate that neuronal-derived DNA is detectable in CSF. Our work is relevant for all diseases featuring death of rare cell-types.

Humans↗
PubMed2005

Levels of 4-aminobiphenyl-induced somatic H-ras mutation in mouse liver DNA correlate with potential for liver tumor development.

The utility of liver H-ras codon 61 CAA to AAA mutant fraction as a biomarker of liver tumor development was investigated using neonatal male mice treated with 4-aminobiphenyl (4-ABP). Treatment with 0.1, 0.3, or 1.0 mumol 4-ABP produced dose-dependent increases in liver DNA adducts in B6C3F(1) and C57BL/6N mice. Eight months after treatment with 0.3 mumol 4-ABP or the DMSO vehicle, H-ras codon 61 CAA to AAA mutant fraction was measured in liver DNA samples (n = 12) by allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). A significant increase in average mutant fraction was found in DNA of 4-ABP-treated mice, with an increase from 1.3 x 10(-5) (control) to 44.9 x 10(-5) (treated) in B6C3F(1) mice and from 1.4 x 10(-5) to 7.0 x 10(-5) in C57BL/6N mice. Compared with C57BL/6N mutant fractions, B6C3F(1) mutant fractions were more variable and included some particularly high mutant fractions, consistent with the more rapid development of liver foci expected in B6C3F(1) mouse liver. Twelve months after treatment, liver tumors developed in 79.2% of 4-ABP-treated and 22.2% of control B6C3F(1) mice; thus measurement of H-ras mutant fraction correlated with subsequent tumor development. This study demonstrates that ACB-PCR can directly measure background levels of somatic oncogene mutation and detect a carcinogen-induced increase in such mutation.

Aminobiphenyl Compounds↗
PubMed2002

QT interval prolongation as a biomarker for torsades de pointes and sudden death in drug development.

Prolongation of the QT interval on the surface 12-lead electrocardiogram is widely accepted as a biomarker for the potential of a drug to produce torsades de pointes and/or sudden death. Detection of drug-induced prolongation of the QT interval in animals and man is frequently confounded by extrinsic and intrinsic factors that limit the ability to detect a true drug effect. In particular drugs that increase heart rate show an apparent increase in QT interval that confounds assessment of a true drug effect on cardiac ventricular repolarization. The basis for the use of the QT interval as a biomarker will be examined.

Animals↗
PubMed1992

Methods and strategies in lung cancer control.

By the Year 2000, deaths related to lung cancer will increase worldwide to 2 million, mainly due to an increase in cigarette smoking by young adults. The control of lung cancer is a multiphased research and application strategy. The identification of cancer risks and causes and the reduction of carcinogen exposure are the first two phases of this strategy. This paper deals with four interventions with a significant potential impact on the consumption of tobacco. (a) A total ban on the sale of tobacco to minors would be one of the most effective measures to reduce the prevalence of smoking among teenagers and would result, in the long run, in a decrease in lung cancer. (b) In developing countries, the production of tobacco is expected to continue to increase until the Year 2000 and to result in a rapid increase in the incidence of lung cancer. (c) The taxation of tobacco is a powerful tool to reduce smoking, especially among teenagers. (d) In order to reduce the incidence of lung cancer, it is crucial that health professionals inform patients about the health consequences of smoking. Cancer chemoprevention, which could reduce the risk of lung cancer among smokers and exsmokers, is an alternative to primary prevention. The very first step in the chemoprevention strategy is to characterize the chemopreventive agents. The investigator can test its inhibitory capacity in vitro or proceed directly to a tumor inhibition study in laboratory animals. Tumor inhibition studies are carried out at the maximum tolerated dose. Compounds which have demonstrated inhibitory activity are then entered in the next phase of the strategy, the study of chemopreventive efficacies. Chemopreventive agents are best classified according to their mechanism in inhibiting the process of carcinogenesis. One of the most promising approaches to cancer chemoprevention is the use of a combination of chemopreventive agents. The National Cancer Institute funded the development of 14 compounds or combinations of compounds as lung cancer chemopreventive agents. Biomarkers of early lesions are generally used to assess the efficacies of the chemopreventive agents in clinical trials. The biomarker should be able to measure the early phase of the carcinogenic process, be relatively inexpensive, and be the least invasive possible. The biomarkers which have been developed for lung cancer are: index of metaplasia of bronchial tissues and exfoliated atypical bronchial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticarcinogenic Agents↗
PubMed2000

Cloning genes whose levels of expression are altered by metals: implications for human health research.

When cells are exposed to toxicants, changes in gene expression ensue. To date, there is little information on gene expression changes induced by metals in mammalian cells. The basic methods for identifying altered gene expression of both a temporary and a permanent nature are outlined, with examples drawn mostly from what is known about metal-induced changes in gene expression. The application of this information in the development of new biomarkers of exposure and effect, in identifying individuals with altered susceptibility to metal compounds, and in the choice of genes for microarrays is discussed.

Biomarkers↗
PubMed2004

High-throughput profiling of dietary polyphenols and their metabolites by HPLC-ESI-MS-MS in human urine.

Polyphenols in biological fluids are generally estimated by HPLC with UV, electrochemical or fluorimetric detection. We describe herein a method specially developed to estimate biomarkers of polyphenol consumption in human urine. We simultaneously quantified 15 polyphenols and their related compounds in human urine using an HPLC coupled with electrospray ionization mass-mass (HPLC-ESI-MS-MS) method with an analytical run time of 6 min. The method has been validated with respect to linearity, precision, and accuracy in intra- and inter-day assays. It has been applied to human urine samples collected from volunteers after consumption of different polyphenol-rich beverages in controlled conditions.

Chromatography, High Pressure Liquid↗
PubMed2005

Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer.

Aberrant promoter methylation of normally unmethylated CpG-islands offers a promising tool for the development of molecular biomarkers. We investigated bronchial aspirates of patients admitted for suspected lung cancer with regard to the prevalence of aberrant methylation of potential marker genes. Applying quantitative methylation specific PCR (QMSP) we analyzed bronchial aspirates from 75 patients with primary lung cancer and 64 bronchial aspirates of patients diagnosed with benign lung disease for promoter methylation of 3 candidate marker genes (p16(INK4a), RARB2 and SEMA3B). Hypermethylation of p16(INK4a) detected 18/75 (24%) cases with primary lung cancer and was present predominantly in squamous cell carcinomas (14/25; 56%). RARB2 QMSP at an assay threshold greater than 30 was found in 42/75 (56%) patients with lung cancer without relation to histological subtype. Patients with benign lung disease showed methylation of p16(INK4a) and a RARB2 QMSP at an assay threshold greater than 30 in 0/64 (0%) and 8/64 (13%) cases, respectively. Combining the 2 methylation markers, p16(INK4a) and RARB2, yielded a sensitivity of 69% and a specificity of 87% for the diagnosis of pulmonary malignancy. In contrast, SEMA3B displayed frequent promoter methylation (around 90%) both in bronchial aspirates of tumor and nontumor cases and thus was not suited as a biomarker. The results of this study indicate that QMSP analysis of p16(INK4a) and RARB2 may aid the diagnosis of primary lung cancer in bronchial aspirates. In particular, detection of p16(INK4a) methylation by QMSP may serve as a highly specific marker of pulmonary squamous cell carcinoma.

Adult↗
PubMed2001

Discovery in toxicology: mediation by gene expression array technology.

Toxicogenomics is a term that represents the merging of toxicology with novel genomics techniques. Data generated in the new-age era of toxicology is relatively complex, requires new bioinformatics tools for adequate interpretation, and allows for the rapid generation of testable hypotheses. Hazard identification and risk assessment processes will advance from the use of genomics techniques, which will lead to greater understanding of mechanism(s) of action of toxicants, development of novel biomarkers of exposure and effect, and better identification of sensitive subpopulations.

Animals↗
PubMed2004

Measurement of fat/water ratios in rat liver using 3D three-point dixon MRI.

Hepatic steatosis, or fatty liver, is commonly observed during the animal phase of drug safety studies. A noninvasive three-dimensional (3D) three-point Dixon method was used to quantitatively evaluate the fatty livers of rats induced by an experimental microsomal transfer protein (MTP) inhibitor, in an effort to develop a safety biomarker that could be translated to human studies. The method was implemented at 2.0 T for in vivo studies, and at 7.1 T for higher-resolution magnetic resonance (MR) histologic studies. In three separate protocols to study dose response and longitudinal evolution, intrahepatic fatty accumulation was detected by this method and confirmed by chemical and histologic assessments. Consistent with the pathologic changes, the fat/water ratios estimated by the MR technique increased significantly at doses of 1 mg/kg and 100 mg/kg of MTP inhibitor after 14 days of continuous administration. Among the more important findings were: 1). with the 3D three-point Dixon method, in vivo longitudinal studies of liver fat distribution can be conducted at significantly higher resolution than has previously been reported; 2). MR histology allows delineation of distribution at the microscopic scale of 0.0024 mm(3) resolution; and 3). the 3D three-point Dixon technique provides relative estimates of liver fat content and distribution at a high confidence level. This technique will be applicable in future studies in which fatty liver is a potential safety issue.

Adipose Tissue↗
PubMed2006

Identification of S-nitrosylated proteins after chronic exposure of colon epithelial cells to deoxycholate.

Apoptosis resistance, a condition favoring genomic instability, is associated with higher risk of colorectal cancer. Deoxycholate (DOC) is a hydrophobic bile salt found in high concentrations in colon cancer patients, and induces apoptosis in cultured colonic cells and ex vivo in colonic biopsies. We showed previously that the chronic exposure of colon cancer cells to increasing concentrations of DOC leads to apoptosis resistance, and the suggested mechanism involves oxidative/nitrosative stress. Nitric oxide (NO) is a key signaling molecule that regulates cell function in a variety of physiologic and pathophysiologic states. In part, NO exerts its actions by S-nitrosylation of target thiols, and several proteins are regulated through this PTM, including the caspases, the main effectors of apoptosis. Here, we performed a proteomics study in the DOC-induced apoptosis-resistant colon cell line, HCT-116RC. Its profile of S-nitrosylated proteins was compared to a control cell line not exposed to DOC. Eighteen differentially S-nitrosylated proteins were identified in the HCT-116RC cell line, 14 of these are novel targets of S-nitrosylation not previously reported. These proteins include cytoskeletal and signaling proteins, metabolic enzymes, chaperones, and redox- and differentiation-related proteins. These results broaden our knowledge of potential signal transduction pathways that may lead to the development of new biomarkers and therapy targets.

Apoptosis↗
PubMed1997

Chemical modification of deoxycytidine at different sites yields adducts of different stabilities: characterization of N3- and O2-deoxycytidine and N3-deoxyuridine adducts of butadiene monoxide.

Eight adducts were characterized from the reaction of deoxycytidine with the chemical carcinogen, butadiene monoxide (BM). They were identified as diastereomeric pairs of N3-(2-hydroxy-3-buten-1-yl)deoxycytidine, N3-(2-hydroxy-3-buten-1-yl)deoxyuridine, N3-(1-hydroxy-3-buten-2-yl)deoxyuridine, and O2-(2-hydroxy-3-buten-1-yl)deoxycytidine based on UV spectra, 1H NMR, FAB/MS, and stability studies. The N3-(2-hydroxy-3-buten-1-yl)deoxycytidine adducts were unstable at pH 7.4, 37 degrees C, and deaminated to the corresponding N3-deoxyuridine adducts with half-lives of 2.3 and 2.5 h. The N3-(1-hydroxy-3-buten-2-yl)deoxycytidine diastereomers were not detected, apparently because of faster rates of deamination compared to the N3-(2-hydroxy-3-buten-1-yl)deoxycytidine adducts. The corresponding four N3-deoxyuridine adducts were stable for up to 168 h. The O2-deoxycytidine adducts were unstable and decomposed with a half-life of 11 h. The N3-(2-hydroxy-3-buten-1-yl)deoxycytidine adducts were initially the major adducts formed upon reaction of deoxycytidine with BM at 37 degrees C in phosphate buffer (pH 7.4), but the corresponding N3-deoxyuridine adducts showed a lag in formation due to the time needed for deamination. The N3-(1-hydroxy-3-buten-2-yl)deoxyuridine and O2-deoxycytidine adducts had linear formation rates, but were formed to a lesser extent. Heating the reaction mixture at 80 degrees C for 1 h converted all N3-deoxycytidine adducts to the stable N3-deoxyuridine adducts. Incubation of deoxycytidine with an excess of BM at pH 7.4, 37 degrees C, followed by the extraction and heating steps allowed calculation of the pseudo-first-order kinetic rate constants for the four uridine adducts. If the heating step was eliminated, then the pseudo-first-order kinetic rate constants could be calculated for the N3-(2-hydroxy-3-buten-1-yl)deoxycytidine and O2-(2-hydroxy-3-buten-1-yl)deoxycytidine adducts. The rate constants for N3-(2-hydroxy-3-buten1-yl)deoxycytidine and the corresponding N3-(2-hydroxy-3-buten-1-yl)deoxyuridine were five- to sixfold the rate constants for the N3-(1-hydroxy-3-buten-2-yl)deoxyuridine and O2-(2-hydroxy-3-buten-1-yl)deoxycytidine adducts. Thus, the results show that the reaction of deoxycytidine with BM yields adducts at different sites with different rates of formation and stabilities. Understanding the chemical interactions of deoxycytidine with BM and the stability of the various adducts may contribute to a better understanding of the molecular mechanisms of mutagenesis and carcinogenesis of BM and the development of useful biomarkers of exposure.

Carcinogens↗
PubMed2000

Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy.

Exposure to a variety of agricultural, industrial, and pharmaceutical chemicals produces nerve damage classified as a central-peripheral distal axonopathy. Morphologically, this axonopathy is characterized by distal axon swellings and secondary degeneration. Over the past 25 years substantial research efforts have been devoted toward deciphering the molecular mechanisms of these presumed hallmark neuropathic features. However, recent studies suggest that axon swelling and degeneration are related to subchronic low-dose neurotoxicant exposure rates (i.e., mg toxicant/kg/day) and not to the development of neurophysiological deficits or behavioral toxicity. This suggests these phenomena are nonspecific and of uncertain pathophysiologic relevance. This possibility has significant implications for research investigating mechanisms of neurotoxicity, development of exposure biomarkers, design of risk assessment models, neurotoxicant classification schemes, and clinical diagnosis and treatment of toxic neuropathies. In this commentary we will review the evidence for the dose-related dependency of distal axonopathies and discuss how this concept might influence our current understanding of chemical-induced neurotoxicities.

Animals↗
PubMed2005

Chemoprevention of lung cancer.

Lung cancer remains a major cause of mortality worldwide, despite advances in surgery, radiotherapy and chemotherapy. Most patients present with advanced disease, and early detection approaches are still experimental. Chemoprevention strategies are therefore essential. Chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress or prevent progression to invasive cancer. The present review will provide an update on lung cancer clinical chemoprevention trials as well as the molecular basis of lung carcinogenesis. A better knowledge of lung carcinogenesis is obviously fundamental to improve chemoprevention strategies. Identification of molecular defects involved in premalignant lesions and/or invasive cancer could lead to clinical studies with new molecular-targeted agents (mainly tyrosine kinase inhibitors, farnesyl-transferase inhibitors and/or antiangiogenic molecules) and the development of surrogate biomarkers. Such biomarkers would be essential to detect high-risk patients, select adequate chemoprevention strategies and monitor drug efficacy. New chemoprevention trials are planned with collaborative efforts of researchers involved in fundamental or clinical studies.

Anticarcinogenic Agents↗