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PubMed2026

Microbial DNA analysis of paired blood-bronchoalveolar lavage fluid in post-HSCT patients with pneumonia implying application conditions of blood as a surrogate in pathogen detection.

BACKGROUND: Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing's simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens. RESULTS: Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients' BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients' blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with > 70% certainty. CONCLUSION: Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.

Humans↗
PubMed2006

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women.

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30-40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1], more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

Adipose Tissue↗
PubMed2005

Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers.

BACKGROUND: Non-small-cell lung cancer arising in never-smokers is usually of adenocarcinoma subtype. The oncogenic pathway of such tumors is poorly understood. To better define the biological characteristics of these tumors, we have compared the expression of a panel of epidermal growth factor receptor (EGFR)-related biomarkers in lung adenocarcinomas from smokers versus those in never-smokers. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed EGFR, pAKT, PTEN, Ki-67, p27 and hTERT expression in specimens from 190 patients with completely resected lung adenocarcinomas (43 never-smokers and 147 smokers). These analyses were performed on tissue microarrays. RESULTS: EGFR expression was higher in tumors from smokers (P < 0.01), while pAKT was overexpressed mainly in tumors from never-smokers (P = 0.01). As expected, the tumors from smokers presented a higher expression of Ki-67 and a more frequent loss of expression of p27 (P < 0.01). In a multivariate model, two biological factors (p27 and Ki-67) and two clinical factors (age and sex) showed independent significant correlation with never-smoking status. CONCLUSIONS: Lung adenocarcinomas in never-smokers have a very distinct immunohistochemical expression profile of EGFR-related biomarkers as compared with lung adenocarcinomas in smokers. High levels of EGFR and Ki-67 are observed in smokers, while never-smokers are characterized by high levels of pAKT and p27.

Adenocarcinoma↗
PubMed2026

FGF19 as a site-specific candidate biomarker in colorectal neuroendocrine carcinomas.

PURPOSE: Gastrointestinal neuroendocrine carcinomas (GI-NECs) are aggressive tumors with marked site-specific heterogeneity, yet molecular markers for colorectal origin are lacking. This study characterized genomic and protein expression profiles to identify origin-specific biomarkers. METHODS: Nineteen GI-NECs (7 esophageal, 6 gastric, 6 colorectal) were analyzed by targeted next-generation sequencing (NGS) of 425 genes and immunohistochemistry (IHC). Genetic variations across primary sites were compared, and associations between FGF19 expression, clinicopathological features, microsatellite (MS) status, and tumor mutational burden (TMB) were assessed. FGF19 transcriptional expression was further examined in The Cancer Genome Atlas (TCGA) colorectal cohort using the UALCAN platform. RESULTS: A total of 163 genomic alterations were identified. FGF19 was the only gene showing site-specific alterations, being exclusively mutated or amplified in colorectal NECs (50%, 95% CI: 11.8-88.2%) with significantly elevated protein expression (83.3%, 95% CI: 35.9-99.6%) compared with other sites. A microsatellite instability-high (MSI-H) subgroup (10.5%, 95% CI: 1.3-33.1%) exhibited markedly higher TMB. TCGA data confirmed upregulated FGF19 in colorectal tumors but showed no survival association, consistent with the prognostic neutrality in our cohort. CONCLUSIONS: FGF19 may act as a site-specific candidate biomarker for colorectal NECs, with 83.3% protein positivity and exclusive site-specific alterations in 50% of cases. Detection of MSI-H suggests that mismatch repair (MMR) testing may be considered in selected patients with suggestive clinical or family histories to inform immunotherapy decisions.

FGF19↗
PubMed2026

Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analysed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain to reveal pertinent mechanisms. We show that common PD risk variants at the serine palmitoyltransferase small subunit B (SPTSSB) locus, a key regulator of de novo sphingolipid biosynthesis, are associated with increased SPTSSB brain expression and elevated plasma ceramides. Additional analyses strongly support our hypothesis that a common SPTSSB causal variant is responsible for PD risk as well as the expression and metabolic quantitative trait loci. Multiple sphingolipids and fatty acid derivatives were perturbed in PD, and we identified both unique and shared features with the Alzheimer's disease metabolome. A PD acylcarnitine signature was further replicated in human post-mortem brain tissue, when comparing those with or without preclinical Lewy body pathology. Integrated analysis of complementary brain proteomic profiles revealed dysregulation of mitochondrial processes dependent on acylcarnitines, including fatty acid beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation. Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD.

Humans↗
PubMed2006

Genomics of hepatitis B and C infections: diagnostic and therapeutic applications of microarray profiling.

Microarray profiling offers many potential advances in diagnostic and therapeutic intervention in human disease because of its unparalleled ability to conduct high-throughput analysis of gene expression. However, limitations of this technique relate in part to issues regarding the various methodologies and experimental designs as well as difficulties in the interpretation of results. Despite this, microarray profiling has led to a better understanding of the molecular pathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Key events in clearance and the development of chronicity of HCV have been identified that may prove to have a role in the development of future treatments. In addition, pharmacogenomic studies of interferon-based treatment for chronic HCV and HBV have provided mechanistic insights into the therapeutic action of interferons. These advances have implications with respect to the development of improved therapeutic agents. New biomarkers for cancer screening and gene profiles with prognostic value for survival have also been developed for hepatocellular carcinoma, which frequently complicates chronic viral hepatitis. Thus, microarray profiling offers enormous potential for improvements in antiviral therapy and our understanding of blood-borne viral hepatitis.

Animals↗
PubMed2006

Short- and long-term risk stratification in acute coronary syndromes: the added value of quantitative ST-segment depression and multiple biomarkers.

OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. BACKGROUND: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. METHODS: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. RESULTS: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). CONCLUSIONS: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.

Aged↗
PubMed1989

Characterization of the bacterial population structure in an anaerobic-aerobic activated sludge system on the basis of respiratory quinone profiles.

Bacterial respiratory quinones were used as biomarkers for studying the bacterial population structure, especially the content of Acinetobacter species, in a laboratory-scale anaerobic-aerobic activated sludge system and in the standard aerobic system. All tested sludges contained both ubiquinone and menaquinone, with a molar ratio of about 1:0.5. High-performance liquid chromatography showed that ubiquinone with eight isoprene units (Q-8) was present as the predominant ubiquinone, Q-10 was the second most common type, and Q-9 and other homologs were minor components in the anaerobic-aerobic sludge and the standard aerobic sludge. Bacteriological examination indicated that, in both sludge systems, Q-8-containing bacteria constituted a large proportion of the aerobic heterotrophic bacterial flora, but only a few strains with Q-9 were found. These findings demonstrate that the population of Acinetobacter species, which contain Q-9 as the major quinone, is negligible in those environments. The present results suggest that the introduction of anaerobic conditions into the aerobic batch process has little influence on the bacterial community structure.

Aerobiosis↗
PubMed2026

A GRADE-assessed systematic review and meta-analysis of randomized controlled trials evaluating the effects of olive leaf or olive pomace supplementation on cardiometabolic and anthropometric health markers.

AIMS: Cardiometabolic diseases (CMDs) are major contributors to global morbidity and mortality, and dietary bioactives such as polyphenols may modulate key risk factors. Olive by-products, particularly olive leaves (OL) and olive pomace (OP), are rich in phenolic compounds with antioxidant, anti-inflammatory, and cardiometabolic effects demonstrated across in vitro, preclinical, and clinical studies. DATA SYNTHESIS: This GRADE-assessed systematic review and meta-analysis included 30 randomized controlled trials (n&#x202f;=&#x202f;1726) evaluating OL or OP supplementation on 21 standardized biomarkers, encompassing inflammatory markers, lipid profile, glycemic control, insulin sensitivity, anthropometric measures, and blood pressure. Meta-analyses were conducted using random-effects models, with effect sizes calculated as mean differences (or standardized mean differences for oxLDL). Between-study heterogeneity was assessed with I2 statistics, and sensitivity and subgroup analyses explored potential sources of variability. Publication bias was evaluated using Begg's test and funnel plots where appropriate. OL supplementation significantly improved lipid parameters (total cholesterol, triglycerides, LDL-C, ApoB, oxLDL) and increased ApoA1, while reducing TNF-&#x3b1;, systolic and diastolic blood pressure, body weight, and BMI. No significant effects were observed on glycemic markers. OP supplementation showed no consistent cardiometabolic benefits and was associated with an increase in IL-8. Certainty of evidence ranged from very low to high, with several outcomes downgraded due to imprecision, heterogeneity, or limited study numbers. CONCLUSION: These findings support the targeted use of OL as an adjunctive strategy for cardiometabolic risk management. Evidence for OP supplementation remains limited, underscoring the need for well-powered, high-quality RCTs to clarify its clinical effects.

Humans↗
PubMed2002

Tissue microarray sampling strategy for prostate cancer biomarker analysis.

High-density tissue microarrays (TMA) are useful for profiling protein expression in a large number of samples but their use for clinical biomarker studies may be limited in heterogeneous tumors like prostate cancer. In this study, the optimization and validation of a tumor sampling strategy for a prostate cancer outcomes TMA is performed. Prostate cancer proliferation determined by Ki-67 immunohistochemistry was tested. Ten replicate measurements of proliferation using digital image analysis (CAS200, Bacus Labs, Lombard, IL, USA) were made on 10 regions of prostate cancer from a standard glass slide. Five matching tissue microarray sample cores (0.6 mm diameter) were sampled from each of the 10 regions in the parallel study. A bootstrap resampling analysis was used to statistically simulate all possible permutations of TMA sample number per region or sample. Statistical analysis compared TMA samples with Ki-67 expression in standard pathology immunohistochemistry slides. The optimal sampling for TMA cores was reached at 3 as fewer TMA samples significantly increased Ki-67 variability and a larger number did not significantly improve accuracy. To validate these results, a prostate cancer outcomes tissue microarray containing 10 replicate tumor samples from 88 cases was constructed. Similar to the initial study, 1 to 10 randomly selected cores were used to evaluate the Ki-67 expression for each case, computing the 90th percentile of the expression from all samples used in each model. Using this value, a Cox proportional hazards analysis was performed to determine predictors of time until prostate-specific antigen (PSA) recurrence after radical prostatectomy for clinically localized prostate cancer. Examination of multiple models demonstrated that 4 cores was optimal. Using a model with 4 cores, a Cox regression model demonstrated that Ki-67 expression, preoperative PSA, and surgical margin status predicted time to PSA recurrence with hazard ratios of 1.49 (95% confidence interval [CI] 1.01-2.20, p = 0.047), 2.36 (95% CI 1.15-4.85, p = 0.020), and 9.04 (95% CI 2.42-33.81, p = 0.001), respectively. Models with 3 cores to determine Ki-67 expression were also found to predict outcome. In summary, 3 cores were required to optimally represent Ki-67 expression with respect to the standard tumor slide. Three to 4 cores gave the optimal predictive value in a prostate cancer outcomes array. Sampling strategies with fewer than 3 cores may not accurately represent tumor protein expression. Conversely, more than 4 cores will not add significant information. This prostate cancer outcomes array should be useful in evaluating other putative prostate cancer biomarkers.

Biomarkers↗
PubMed2004

Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics.

Liver cirrhosis is a worldwide health problem. Reliable, noninvasive methods for early detection of liver cirrhosis are not available. Using a three-step approach, we classified sera from rats with liver cirrhosis following different treatment insults. The approach consisted of: (i) protein profiling using surface-enhanced laser desorption/ionization (SELDI) technology; (ii) selection of a statistically significant serum biomarker set using machine learning algorithms; and (iii) identification of selected serum biomarkers by peptide sequencing. We generated serum protein profiles from three groups of rats: (i) normal (n=8), (ii) thioacetamide-induced liver cirrhosis (n=22), and (iii) bile duct ligation-induced liver fibrosis (n=5) using a weak cation exchanger surface. Profiling data were further analyzed by a recursive support vector machine algorithm to select a panel of statistically significant biomarkers for class prediction. Sensitivity and specificity of classification using the selected protein marker set were higher than 92%. A consistently down-regulated 3495 Da protein in cirrhosis samples was one of the selected significant biomarkers. This 3495 Da protein was purified on-chip and trypsin digested. Further structural characterization of this biomarkers candidate was done by using cross-platform matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) peptide mass fingerprinting (PMF) and matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry (MS/MS). Combined data from PMF and MS/MS spectra of two tryptic peptides suggested that this 3495 Da protein shared homology to a histidine-rich glycoprotein. These results demonstrated a novel approach to discovery of new biomarkers for early detection of liver cirrhosis and classification of liver diseases.

Algorithms↗
PubMed2026

Sex Hormone Receptors, HBV Integrations and Their Prognostic Predictive Value Among Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection predominantly affects males, yet few studies have investigated the association between sex hormones and HBV integrations, and their involvement in HCC prognosis. We assessed estrogen receptor alpha (ER&#x3b1;) and androgen receptor (AR) expression via immunohistochemistry on tissue microarrays constructed from 426 HBV-related HCC samples. HBV integration features were determined using HBV-captured sequencing data. Logistic regression models were utilized to evaluate the association between sex hormone receptor expression level and HBV integration features. Cox regression models, combined with machine learning (ML) methods, were implemented to investigate the prognostic value of sex hormone receptors and HBV integrations concerning overall survival. We found high AR expression level was significantly associated with higher HBV integration levels (adjusted odds ratio [aOR]&#x2009;=&#x2009;1.84, 95% confidence interval [CI]: 1.09-3.11, P for trend&#x2009;=&#x2009;0.012), TERT integration (aOR&#x2009;=&#x2009;2.34, 95% CI: 1.16-4.74, P for trend&#x2009;=&#x2009;0.047), intergenic integration (aOR&#x2009;=&#x2009;2.25, 95% CI: 1.20-4.24, P for trend&#x2009;=&#x2009;0.021), and promoter integration (aOR&#x2009;=&#x2009;1.81, 95% CI: 1.00-3.31, P for trend&#x2009;=&#x2009;0.034). The inclusion of sex hormone receptors and HBV integrations in the predictive models led to improvements across all performance metrics in the Cox regression analyses (AUC improvement: 0.014 [Training], 0.026 [Validation]) and the ML (AUC improvement: 0.022 [Training]), although a slight deterioration in performance was noted in the ML validation set. The results suggested a relationship between AR expression level and HBV integration events, as well as the potential utility of HBV integration biomarkers and sex hormone receptor profiles in assessing post-surgical prognosis among HCC patients.

Humans↗
PubMed2006

Classifications of ovarian cancer tissues by proteomic patterns.

Ovarian cancer is a morphologically and biologically heterogeneous disease. The identification of type-specific protein markers for ovarian cancer would provide the basis for more tailored treatments, as well as clues for understanding the molecular mechanisms governing cancer progression. In the present study, we used a novel approach to classify 24 ovarian cancer tissue samples based on the proteomic pattern of each sample. The method involved fractionation according to pI using chromatofocusing with analytical columns in the first dimension followed by separation of the proteins in each pI fraction using nonporous RP HPLC, which was coupled to an ESI-TOF mass analyzer for molecular weight (MW) analysis. A 2-D mass map of the protein content of each type of ovarian cancer tissue samples based upon pI versus intact protein MW was generated. Using this method, the clear cell and serous ovarian carcinoma samples were histologically distinguished by principal component analysis and clustering analysis based on their protein expression profiles and subtype-specific biomarker candidates of ovarian cancers were identified, which could be further investigated for future clinical study.

Adenocarcinoma, Clear Cell↗
PubMed2000

Cytochrome P450-dependent monooxygenase activities and their inducibility by classic P450 inducers in the liver, kidney, and nasal mucosa of male adult ring-necked pheasants.

In this study, several P450-dependent monoxygenase activities in the liver, kidney, and nasal mucosa of ring-necked pheasants were examined. In addition, the presence and inducibility of P450 isoenzymes in the hepatic and renal tissues of pheasants were examined by using typical substrates and inducers of P450s along with polyclonal antibodies raised against mammalian isoforms. Anti-rat P450 1A1 recognized in microsomes of both pheasant liver and kidney a protein that was markedly induced by beta-naphthoflavone and accompanied by an increase of various monooxygenases, in particular, methoxyresorufin-O-demethylase (MROD) activity. Anti-rat P450 2E1 revealed in microsomes of the pheasant liver but not in kidney an immunoreactive protein that was slightly induced by acetone but not accompanied by an increase of para-nitrophenol hydroxylase activity. On the other hand, acetone treatment caused an induction of other hepatic monoxygenases including MROD, erythromycin N-demethylase, and 6beta-testosterone hydroxylase. These two latter activities, known to be markers for 3A isoenzymes in rodents, were also enhanced in pheasant liver by phenobarbital but not by dexamethasone. The treatment with these two inducers also lacked to point out hepatic and renal proteins immunorelated to P450 3A or 2B subfamily, suggesting that these isoforms may be not expressed in pheasant. On the other hand, anti-rat P450 2C11 recognized two immunorelated proteins in the liver of both control and treated pheasants. The treatment with clofibrate, a mammalian inducer of 4A subfamily, induced both in liver and kidney of pheasant: i) a protein that cross-reacted with anti rat P450 4A1 and ii) the (omega) and (omega-1) lauric acid hydroxylase activities, known to be associated in mammals to this P450 subfamily. In the nasal mucosa of pheasant, a protein immunorelated to P450 2A and some monooxygenase activities (i.e., 7-ethoxycoumarin O-deethylase) linked, in mammals, to this isoform have been found; by contrast a protein immunoreactive with anti P450 2G1 was not found. In conclusion, the immunochemical properties and monooxygenase activities of constitutive and inducible P450s in pheasants were different not only from those of mammals but also from those of chickens. The findings of the present work also suggest that the P450 induction profiles might provide a potential biomarker of pheasant exposure to chemicals or environmental pollutants in the wild-field or in the stock-farm.

Acetone↗
PubMed2007

Chemical characteristics and source implications of petroleum hydrocarbon contaminants in the sediments near major drainage outfalls along the coastal of Laizhou Bay, Bohai Sea, China.

The associated industrial and urban developments are located to a large extent along the Laizhou Bay, Bohai Sea coastal and raw sewage is often discharged into near shore waters with little treatment. To find out chemical characteristics and pollution source of the petroleum related contaminations in sediments near the major drainage outfalls located in the coastal, in this study, 10 surface sediment samples were collected during June. Sediment samples were extracted by organic solvents, separated by silica gel column chromatography and the concentrations and the profiles of n-alkane, biomarker and PAH in sediments were analyzed by gas chromatography-mass selective detector (GC-MSD). The use of several molecular markers and related indexes derived for n-alkane and PAHs has been proposed for assessing the relative contributions to the environment of hydrocarbon sources. As a result, n-alkanes reflect that the sea area of paper mill (Station ZZ08) is dominated by vascular plant. DY petroleum oil field and outer shore of the paper mill (Station ZZ02) have some degrees of petroleum related hydrocarbon contamination. Whereas the contamination of the sea area of TH River may be ascribed to different sources such as territorial non-point pollution source, domestic sewages, and stormwater runoff. Judged by their PAH ratios, the sediments near the paper mill (Station ZZ02) and the outer station of the oil field (Staion TH2) were pyrolytic. The estuary of Tiao River including the inner Station THX, TH10 and TH05 are petrogenic. The marine sediment near DY drainage outfall may have a mixture source of PAH both pyrolytic and petrogenic.

China↗
PubMed2004

Effects of beta-naphthoflavone, phenobarbital and dichlobenil on the drug-metabolizing system of liver and nasal mucosa of Italian water frogs.

In this study, we have examined the presence and inducibility of phase I and II drug-metabolizing enzymes in the liver and nasal mucosa of Italian water frogs of control and pretreated with beta-naphthoflavone, phenobarbital and dichlobenil by using typical substrates for these enzymes along with polyclonal antibodies mainly raised against mammalian enzymes. The CYP content and various monooxygenase and phase II enzyme activities in the liver of this frog were found similar, when reported, to those of largely aquatic and semiaquatic frogs. The treatment with beta-naphthoflavone resulted in an induction in the liver of a CYP1A and the induction was manifested by (a) immunoblot analysis using anti-rat CYP1A1, (b) an increase of CYP1A-mediated methoxyresorufin-O-demethylase and ethoxyresorufin-O-deethylase activities. The treatments with both phenobarbital and dichlobenil did not produce in the liver any effect on the assayed enzymes. When the nasal mucosa of water frogs was analyzed, various monooxygenase and phase II enzymatic activities, generally comparable to those of liver, were determined. However, by using antibodies anti-three GST different classes, we found a different reactivity into the cytosol of the two tissues indicating a differential tissue susceptibility to toxic effects of xenobiotics. In the nasal mucosa, a protein immunorelated to CYP2A and monooxygenase activities (i.e. ethoxycoumarin-O-deethylase and coumarin-7-hydroxylase) linked in mammals to this isoform have also been found. The treatment of water frogs with the herbicide dichlobenil decreased both the above-mentioned activities and the immunoreactive CYP2A apoprotein. The pretreatment with metyrapone, a CYP inhibitor, protected the CYP2A apoprotein and its linked activities from toxic effect of dichlobenil indicating a key role of this enzyme in the bioactivation of this herbicide. The findings of the present work suggest that the hepatic CYP1A induction and the nasal CYP2A-like inhibition profiles might provide two potential biomarkers of the Italian water frogs exposure to environmental and aquatic pollutants.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2001

Tyrosine kinase inhibitors and signal transduction modulators: Rationale and current status as chemopreventive agents for prostate cancer.

Cell growth and differentiation are processes intimately associated with carcinogenesis and regulated by tyrosine kinases and other signaling proteins. Identification of drugs that target signaling molecules is hampered by both the large number of targets and the complex nature of signaling cascades. Optimal development of chemopreventive agents must take into account affinity for the target, pharmacology, and safety profile of the agent. Validated biomarkers will allow the optimal implementation of chemopreventive trials. Directed epidemiologic studies can lead to the identification of lead compounds for chemoprevention, such as genistein. Therefore, agents targeted to pathways and molecules of known biological importance in the prostate hold the promise of clinical efficacy against prostate cancer in a chemopreventive setting.

Alkyl and Aryl Transferases↗