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PubMed2003

Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers.

An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30 degree C for 20 min (DNA-instability test) has been used as a marker of malignancy. The test was applied to bioptic tissues of human gastric polyp assessed histopathologically as foveolar hyperplastic polyp (13 cases), mild (58 cases), moderate (86 cases), and severe (20 cases) dysplasia, and adenocarcinomas (14 cases). The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor (DFF45), and basic fibroblast growth factor (bFGF). The DNA-instability test was positive in 14 (100%) adenocarcinoma cases, 20 (100%) severe dysplasia cases, 52 (60.5%) moderate dysplasia cases, and 12 (20.7%) mild dysplasia cases, indicating malignancy. All foveolar hyperplastic polyps were negative to the DNA-instability testing. Furthermore, the percentage of glands positive in the DNA-instability test steadily increased in going from mild (10%), to moderate (40%), to severe (100%) dysplasia, and adenocarcinoma (100%). All other biological markers tested in the present study showed significantly higher values in the adenoma glands, being positive to DNA-instability testing, irrespective of the dysplasia grade, as compared to those in the adenoma glands that were negative to DNA-instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. These results indicate that cancer cell clones are already present at the adenoma stages showing a positive DNA-instability test, enhanced proliferative activity, p53 mutation, induction of DFF45 and bFGF. These factors allow cancer cell proliferation, producing heterogeneous subclones due to DNA-instability, enhancing their survival by escaping apoptosis, and providing abundant nutrients during the early-stage progression of gastric cancer. Based on these findings, we herein propose the concept of "procancer" (as opposed to "pre-cancer") as being a unique stage during the course of carcinogenesis and cancer progression. We designate the term to cancer clones at the very early stages of malignant progression that do not show distinguishable morphological atypia but do show positive DNA-instability testing and positive staining for various biomarkers such as Ki67, p53, DFF45, and bFGF. We also define the abnormal positive staining of these biomarkers, including the DNA-instability test as "functional atypia", compared to the ordinary morphological atypia.

Adenocarcinoma↗
PubMed2006

No incremental clinical information of NT Pro BNP at peak exercise over resting levels in patients with impaired left ventricular function.

There is an increasing tension to use NT Pro BNP blood levels at peak exercise testing. Their possible superiority over resting levels in congestive heart failure or factors associated with their increase have not been adequately studied. We studied 65 patients, 51 males and 14 females with impaired left ventricular function. Mean left ventricular ejection fraction (LVEF) was 35+/-9%. Our findings suggest that in patients with heart failure NT Pro BNP plasma levels at peak exercise do not provide incremental clinical information over resting levels. Baseline NT Pro BNP alone can provide sufficient clinical information.

Biomarkers↗
PubMed2004

[Usefulness of biological markers in the evaluation of smoking at the first visit of a smoking cessation program].

INTRODUCTION: We have studied the relationship between urinary cotinine and other tobacco markers to assess the relevance of urinary cotinine in the dosage of nicotine substitutes. METHODS: One hundred and fifty-five patients, who were regular cigarette smokers not taking any nicotine substitutes took part in the study. The parameters examined were daily consumption, nicotine contents of the cigarettes, the Fagerström test score, levels of carbon monoxide (CO) in exhaled breath air and urinary cotinine. RESULTS: The most significant correlation was between urinary cotinine and exhaled CO (Spearman rs=0,59 p<0,001). The correlation between urinary cotinine, the Fagerström test (rs=0,32 p<0,001) and daily cigarette consumption (rs=0,32 p<0,001) was less significant. The nicotine content was not related to urinary cotinine (rs =-0,10NS). CONCLUSIONS: For economic reasons measuring urinary cotinine is not necessary when the CO level is or=35 ppm. It becomes useful if the CO level is between 15 and 34 ppm, as CO level in itself is insufficient to determine the dosage of nicotine substitutes.

Adolescent↗
PubMed2006

Free 3-nitrotyrosine in exhaled breath condensates of children fails as a marker for oxidative stress in stable cystic fibrosis and asthma.

3-Nitrotyrosine (3-NT) is considered as a marker of oxidative stress, which occurs during inflammation. Since 3-NT levels in exhaled breath condensate (EBC) are very low, we applied a specific and sensitive gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) method and high performance liquid chromatography (HPLC) with electrochemical detection for the analysis of free 3-NT in EBC. A total of 42 children (aged 5-17 years) were enrolled in this study, including children with asthma (n=12), cystic fibrosis (n=12), and healthy controls (n=18). Additionally, 14 healthy non-smoking adults (aged 18-59 years) were included. An EcoScreen system was used for the collection of EBC samples. Free 3-NT levels in EBC ranged from 0.54-6.8 nM. Median (interquartile range) concentrations (nM) were similar in all groups: 1.46 (0.97-2.49) in healthy adults, 2.51 (1.22-3.51) in healthy children, 1.46 (0.88-2.02) in children with asthma, and 1.97 (1.37-2.35) in CF children, respectively (p=0.24, Kruskall-Walis test). No difference was found between the children with airway disease and age-matched healthy controls. In healthy subjects, there was no effect of age on 3-NT concentrations. HPLC analyses provided similar concentration ranges for EBC 3-NT when compared with GC-NICI-MS. Our study has clearly demonstrated that free 3-NT in EBC fails as a marker for oxidative stress in children with stable CF and asthma.

Adolescent↗
PubMed2006

Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence.

PURPOSE: Cervical cancer is the second most frequently diagnosed cancer in women worldwide. About one-third of patients experience recurrent disease. A better chance of survival might be achieved by the early detection of recurrent cervical cancer. [(18)F]fluoro-2-deoxy-D-glucose (FDG) PET could be a promising imaging modality for this purpose, given that FDG PET has high diagnostic efficacy. Ideally, pre-selection of patients should be performed before considering FDG PET. The purpose of this study was to investigate parameters of primary cervical cancer associated with recurrence as a basis for pre-selection of patients in whom FDG PET should be performed. METHODS: Thirty-eight cervical cancer patients, clinically suspected of having recurrent disease, underwent FDG PET. Tissue from primary tumours and nine histologically confirmed metastases was analysed for biomarkers possibly related to glucose metabolism and prognosis (vascular endothelial growth factor, CD31 for microvessel density, glucose transporter-1, hexokinases I, II and III, Ki67, p53, hypoxia-inducible factor 1alpha, and degree of infiltration by lymphocytes and macrophages). RESULTS: Based on clinical outcome, sensitivity and specificity of FDG PET were 96% and 100%, respectively. Cox regression revealed microvessel density and p53 (tumour suppressor protein) to be the two most important biomarkers for prediction of recurrence (hazard ratios 2.54 and 2.28, respectively). By combining these two biomarkers in a parallel test, sensitivity and specificity in predicting recurrence were 87% and 71%, respectively. Leave-one-out cross-validation demonstrated predictive validity of a model based on microvessel density and p53. CONCLUSION: In this first study of its kind, we have demonstrated that microvessel density and p53 profiles could be important in pre-selecting cervical cancer patients for detection of recurrence by FDG PET.

Adult↗
PubMed2006

Exhaled breath condensate pH standardised for CO2 partial pressure.

Exhaled breath condensate (EBC) pH is considered to reflect the acid-base balance of the airways. Current pH measurements do not take into account the effect of CO2. The aim of the present study was to determine the effect of condensate CO2 partial pressure on pH and to provide a more precise mode of EBC pH determination. Condensate pH and CO2 partial pressure were measured in parallel from 12 healthy volunteers and 12 asthmatics using a blood gas analyser in neat, argon de-aerated and CO2-loaded samples. The regression analysis was used to test the relationship between pH and CO2, and to calculate the pH at a CO2 level of 5.33 kPa (physiological alveolar CO2 partial pressure). Reproducibility of different pH readings was compared using the Bland-Altman test. Condensate CO2 concentration was variable both in neat and argon de-aerated samples. There was a close negative logarithmic relationship between CO2 and pH. Calculation of pH at a CO2 level of 5.33 kPa provided reproducibility approximately six times as good as that of the currently used measurements. Condensate CO2 partial pressure influences pH measurements. Determination of pH at a standard CO2 level provides the most reproducible condensate pH values to date.

Acid-Base Equilibrium↗
PubMed2004

[Acquired von Willebrand syndrome with autoimmune hemolytic anemia].

A 17-year-old female underwent examination due to the chief complaints of epistaxis and bleeding from the gums. In addition to hemolytic anemia (Coombs positivity), she was found to have a marked reduction in the von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo). Anti vWF antibodies mainly comprised of IgG1 fractions were also detected, so acquired von Willebrand syndrome (AvWS) with autoimmune hemolytic anemia (AIHA) was diagnosed. The recovery of vWF:Ag and vWF:RCo following administration of a factor VIII concentrate containing vWF was good, but the half life was short at about two hours and the collagen binding activity and vWF:RCo in mixing tests with control plasma were only mildly inhibited. Therefore, the anti vWF antibody in the present case was thought not to inhibit vWF function but to be involved in clearance promotion. Hemostatic control during hemorrhage was performed using a factor VIII concentrate containing vWF. With the administration of prednisolone thereafter, anti vWF antibodies disappeared at the same time as there was improvement in the AIHA. Throughout the course the patient contracted acute hepatitis A, became pregnant and gave birth, but there were no clear effects on the clinical phenotype of AvWS.

Adolescent↗
PubMed2006

Associations between antioxidant status, markers of oxidative stress and immune responses in allergic adults.

BACKGROUND: There has been growing interest in the role of antioxidant function in controlling inflammatory disease states, such as allergy. This study investigated the relationship between antioxidant status, markers of airways inflammation [exhaled nitric oxide (eNO)], oxidative stress (F(2) isoprostanes) and immune responses in allergic adults. METHODS: Antioxidants (vitamins C, E, beta-carotene and selenium) and total antioxidant capacity (tAC) in serum were examined in relation to eNO, plasma F(2) isoprostanes and peripheral blood mononuclear cell (PBMC) cytokine and lymphoproliferative response to house dust mite (HDM) allergen, Staphylococcus enterotoxin B (SEB), phytohaemaglutinin (PHA) and lipopolysaccharide (LPS) in 54 allergic adults. RESULTS: Firstly, levels of specific vitamins did not correlate with tAC. Secondly, we did not see any evidence that specific vitamin levels (or tAC) were associated with either polarization or attenuation of in vitro immune responses. If anything, there were positive correlations between antioxidant (vitamin C and selenium) levels and HDM allergen responses [lymphoproliferation (selenium; r=0.35, P=0.013) and both Th2 IL13 (vitamin C; tau=0.254, P=0.028) and Th1 IFN-gamma (vitamin C; tau=0.302, P=0.009) responses]. There were also significant positive relationships between antioxidant levels and IL-10 responses to polyclonal stimulation by SEB (r=0.292, P=0.036) and LPS (r=0.34, P=0.015) (beta-carotene) and PHA (r=0.34, P=0.021) (tAC). Thirdly, although airways inflammation (eNO) was associated with both in vitro and in vivo (skin test reactivity) to HDM, we did not see any correlation between eNO and oxidative stress (F(2)-isoprostanes). Finally, there were no consistent relationships between oxidative stress and immune responses. CONCLUSION: There was no evidence that higher antioxidant levels were associated with reduced allergen responsiveness in allergic adults. If anything, antioxidant status was associated with increased immune responsiveness. The significance of this needs to be addressed in future intervention studies.

Adult↗
PubMed1999

Induction of micronuclei in human lymphocytes by organic solvents in vitro.

Our work is focused on identifying micronuclei (MN) induced in whole blood lymphocyte cultures after treatment with the organic solvents toluene, benzene, and acetone. We used the micronucleus test as a cytogenetic biomarker for genotoxicity and treated whole blood cultures with different concentrations of these solvents (0.1 to 5 mM) and mixtures of them (toluene plus acetone, toluene plus benzene). Our results did not show a significant increase in the number of micronuclei in binucleated lymphocytes after 48 hr of in vitro treatment. The addition of an external metabolic factor (10% S9 mix for 2 hr) in blood cultures treated with the organic solvents or their mixtures did not cause induction of MN. These results indicate the lack of genotoxic activity of toluene, benzene, and acetone in vitro.

Acetone↗
PubMed2002

Effect of Helicobacter pylori infection on fibrinogen level in elderly patients with ischaemic heart disease.

BACKGROUND: Fibrinogen is an important risk factor for ischaemic heart disease (IHD) (1) and an elevated fibrinogen level has been reported in younger patients infected with Helicobacter pylori (H pylori) infection (2, 3). However, the effect of Helicobacter pylori infection on fibrinogen level in elderly population with IHD is not known. Also in particular the effect on fibrinogen with eradication of Helicobacter pylori has not been previously reported. The aim of this study was to investigate the influence of H pylori on fibrinogen levels in elderly patients with IHD and to assess the effect of eradication therapy on fibrinogen levels. PATIENTS AND METHODS: Forty patients over the age of 65 years presenting with symptomatic IHD and an age-matched control group of 21 patients were studied. The 14-C urea breath test was used for detecting H pylori infection. Patients found to be H pylori positive were treated with omeprazole 40 mg daily and amoxicillin 500 mg three times daily for 14 days. Fibrinogen concentration was measured at the beginning of treatment and repeated at 4 weeks after completion of treatment along with the urea breath test in those tested positive for H pylori and fibrinogen level was repeated at 6 weeks in the H pylori negative patients. RESULTS: The prevalence of H pylori infection was 19/40 (47.5%) in the IHD group and 9/21 (42.8%) in the control group. The median serum fibrinogen level was 4.34 g/l (3.73-6.04 i.q. range) in H Pylori positive patients and 4.86 g/l (3.58-6.11 i.q. range) in H Pylori negative patients in both the IHD and age-matched control group, with no significant difference between the two groups, p = 0.78 (Mann-Whitney test). In the IHD group 27/40 (67.5%) had a fibrinogen level >4.0 g/l compared to 11/21 (52.3%) in the control group. The median fibrinogen level decreased significantly from 5.75g/l (i.q. range 4.39-6.71) to 4.41 g/l (i.q. range 3.80-6.06) after eradication treatment of H pylori in patients with raised fibrinogen levels (p < 0.01). CONCLUSION: The presence of H Pylori infection did not correlate with the presence of IHD, and the fibrinogen level was not raised in the IHD group. However, in elderly patients with H pylori infection, eradication therapy lowered fibrinogen levels in those with elevated (>4.0 g/l) fibrinogen level.

Aged↗
PubMed1999

Alloreactivity and association of human natural killer cells with the major histocompatibility complex.

All NK cells potentially lytic for autologous cells but not expressing self-major histocompatibility complex (MHC)-reactive receptors could be eliminated by a negative selection mechanism during ontogeny. This idea is based on the existence of a NK cell subset expressing a specific inhibitory receptor for allogeneic MHC alleles. As ancestral haplotypes of the MHC appear to define identical MHC haplotypes in unrelated individuals, unrelated individuals having the same ancestral haplotype should also have the same NK-defined allospecificities that have been shown to map to the human MHC. To test this prediction, multiple cell lines from unrelated individuals having the same ancestral haplotypes were tested for the NK-defined allospecificities. It was found that cells having the same ancestral haplotypes do have the same NK-defined specificities. Furthermore, the NK-defined phenotype of cells that possess two different ancestral haplotypes can be predicted from the NK-defined phenotypes of unrelated cells that are homozygous for the ancestral haplotypes concerned. Although the group 1 and 2 NK-defined allospecificities can be explained to some extent by HLA-C alleles, evidence is presented that additional genes may modify the phenotype conferred by HLA-C.

Alleles↗
PubMed2002

Exhaled hydrogen peroxide, nitrite and nitric oxide in healthy children: decrease of hydrogen peroxide by atmospheric nitric oxide.

Hydrogen peroxide (H2O2) and nitrite (NO2-) in exhaled breath condensate have recently been suggested as non-invasive markers of airway inflammation. The goal of this study was to clarify the role of factors that may potentially influence the measurement of H2O2 and nitrite and to look for possible correlations among these inflammatory markers. H2O2 and nitrite values were assessed fluorometrically in breath condensate of 102 healthy children (age 4-18 years) and a detailed status of atopy (including history, lung function and skin prick test) was taken in all children. To find out the role of atmospheric nitric oxide, eNO and envNO were measured via chemiluminescence in association with the sampling of the breath condensate. Median (interquartile range) H2O2 was 0.51 (0.26 - 0.74) microM and nitrite was 3.3 (2.7 4.1) microM. A significant negative correlation between H2O2 and envNO was observed (r = -0.50; p < 0.0001). ENO was independent of envNO at our envNO range up to 56 ppb. No further correlation was found. The inflammatory markers in exhaled breath condensate H2O2, nitrite and eNO are not interrelated to each other in healthy children. Whereas eNO was not dependent on envNO values, high envNO values must be taken into account when measuring H2O2 in exhaled breath condensate.

Adolescent↗
PubMed2004

Breath analysis in critically ill patients: potential and limitations.

Breath tests are attractive since they are noninvasive and can be repeated frequently in the dynamically changing state of critically ill patients. Volatile organic compounds can be produced anywhere in the body and are transported via the bloodstream and exhaled through the lung. They can reflect physiologic or pathologic biochemical processes such as lipid peroxidation, liver disease, renal failure, allograft rejection, and dextrose or cholesterol metabolism. This review describes the diagnostic potential of endogenous organic volatile substances in the breath of critically ill patients. Since many of these patients require ventilatory support, aspects of breath analysis under mechanical ventilation will be addressed. Analytical procedures, problems concerning the physiologic meaning of breath markers and future developments will be discussed.

Biomarkers↗
PubMed1996

Carbohydrate-deficient transferrin as a marker of alcohol intake: a study with healthy subjects.

This paper reports the results of a 3-week drinking experiment in 51 healthy male subjects, examining the value of %CDT (carbohydrate-deficient transferrin) in the context of different levels of alcohol intake. All healthy persons were urine-tested drug-free and underwent daily breath alcohol tests for the 7 days preceding, and during the whole 3 weeks of, the experiment. Subjects were divided into five groups, consuming different amounts of alcohol daily over a 3-h period in the presence of the investigators. The five groups consisted of 10, 9, 10, 16 and 6 subjects respectively and consumed a daily dose of ethanol of 20, 40, 60, 80 and 80 g respectively for 3 weeks. No significant changes in %CDT were detected in most subjects, even in the 80 g alcohol-consuming groups. The results suggest that CDT is not sensitive for the detection of short-term heavy drinking by healthy subjects.

Adult↗
PubMedDate not supplied

The parallelogram approach in studies of genotoxic effects.

Over the past two decades mutagenicity tests have been used for the identification of potential human mutagens and have had an ancillary role, as supportive evidence in the assessment of human carcinogens. The demonstration of human germinal mutagens has been beyond the main scope of short-term testing strategies. However, just as mutagenicity tests have been useful in detecting potential carcinogens so should carcinogenicity tests assist the identification of presumptive germ cell mutagens. Cancer is an easily observable phenotype of mutation for genotoxic carcinogens and multi-site carcinogens or gonadal carcinogens logically could be germ cell mutagens. Thus carcinogenicity and mutagenicity data for a given genotoxic chemical should be considered together in the identification of putative germinal mutagens. Clearly, most classified human carcinogens are genotoxic thus helping to build the case for human germ cell mutagenicity. This paper describes the issues involved in such thinking and suggests an enhanced parallelogram approach incorporating the cancer endpoint. The enhanced parallelogram is explored using 1,3-butadiene and ethylene oxide as examples. The obvious lack of data for extrapolations using the parallelogram method suggests the need for targeted studies specifically designed for use in this approach.

Animals↗
PubMed2004

Exhaled nitric oxide: relation to sensitization and respiratory symptoms.

BACKGROUND: Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation. OBJECTIVE: To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross-sectional study of the respiratory health of bleachery workers. METHODS: Two hundred and forty-six non-smoking bleachery and paper-mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop trade mark test. RESULTS: The atopic and the non-atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non-atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens. CONCLUSION: The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.

Adult↗
PubMed2002

Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients.

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 m. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean +/- SEM, 42.9 +/- 6.9 vs 43.3 +/- 6.6 ppb) and non-asthmatic (13.3 +/- 1.3 vs 13.7 +/- 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

Analysis of Variance↗
PubMed2001

Colonic mucosal prostaglandin E2 and cyclooxygenase expression before and after low aspirin doses in subjects at high risk or at normal risk for colorectal cancer.

UNLABELLED: Development of potential cancer chemopreventive drugs involves the systematic evaluation of these drugs in preliminary Phase I and II studies in human beings to identify the optimal drug dose, drug toxicity, and surrogate end point biomarker modulation. OBJECTIVES: We tested the hypothesis that aspirin, at a single, once-daily 81-mg dose, will reduce colonic mucosal concentration of prostaglandin estradiol (E2) in individuals at high risk for colorectal cancer development similar to our prior observations in a young normal-risk population. METHODS: Aspirin was administered at a dose of 81 mg once daily for 28 days in a cohort of 92 matched high-risk and normal-risk colorectal cancer subjects. Prostaglandin E2 and cyclooxygenase expression were assayed from distal sigmoid biopsies from all of the subjects before and after treatment. RESULTS: The mean prostaglandin E2 for normal-risk subjects before aspirin treatment was 11.3 +/- 1.7 pg/microg (mean +/- SE) tissue protein and after aspirin treatment was 4.9 +/- 0.91 pg/microg tissue protein (P < 0.0001). In high-risk subjects, mean pretreatment prostaglandin E2 was 14.4 +/- 1.7 pg/microg tissue protein and after aspirin treatment was 4.7 +/- 0.70 pg/microg tissue protein (P < 0.0001). Aspirin treatment did not alter cyclooxygenase-1 protein expression. CONCLUSIONS: Aspirin treatment at a dose of 81 mg reduces colorectal mucosal prostaglandin E2 concentration after 28 daily doses. Risk for colorectal carcinoma did not modify colorectal mucosal baseline or post-aspirin prostaglandin E2, or cyclooxygenase expression. Colorectal mucosal prostaglandin concentration may be used as a "drug-effect surrogate biomarker," that is, a surrogate to assess sufficient delivery and tissue effect of a chemopreventive agent.

Adult↗