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At least 667 records · Page 37Linked to original sources
PubMed2003

Dysregulation of the annexin family protein family is associated with prostate cancer progression.

Hormone refractory prostate cancer (PCa) is invariably lethal despite aggressive clinical treatment strategies. Detection strategies are needed to identify aggressive PCa before it becomes widely disseminated. Recently, two studies identified annexin 1 and 7 as potential biomarkers in the development of PCa progression. The annexins are a group of calcium-binding structural proteins that may play a role in the regulation of membrane trafficking, cellular adhesion, and cell signaling. Therefore the goal of this study is to simultaneously characterize the multiple members of the annexin family of genes in advanced PCa. Prostate samples from men with advanced hormone refractory PCa were compared to samples of hormone-naïve PCa and noncancerous prostate tissue. Samples from 15 patients with advanced hormone refractory PCa were used. To examine the annexin family, gene expression profiles from 21 noncancerous prostate tissues, 16 clinically localized PCas, and 20 hormone refractory PCa samples were used. By cDNA microarray analysis, annexins 1, 2, 4, 7, and 11 were significantly decreased in hormone refractory PCa when compared to localized hormone-naïve PCa with 2.2-, 1.5-, 1.3-, 1.4-, and 1.8-fold decreases, respectively (all P values <0.05). Interstudy validation of annexin family transcript expression was performed by meta-analysis of three other published prostate profiling studies. High-density tissue microarrays were used to validate a subset of annexins at the protein level by immunohistochemistry. Tissue microarray analysis revealed a significant decrease in protein expression for annexins 1, 2, 4, 7, and 11 in hormone refractory PCa as compared to localized PCa with 1.68-, 2.46-, 2.52-, and 3.01-fold decreases, respectively (Kruskal Wallis test, all P values P < 0.05). However, no significant differences were detected between the clinically localized PCa and noncancerous prostate tissues. These findings suggest that down-regulation of several members of the annexin family may contribute to PCa tumorigenesis. Annexins 1, 2, 4, 7, and 11 may play a role in tumor progression through distinct mechanisms or, alternatively, they may have redundant tumor suppressor activities. This study also suggests that a meta-analysis of existing gene expression data is useful in confirming findings from individual studies. Finally, down-regulation of several annexin family members may play a role in the development of the lethal PCa phenotype.

Adult↗
PubMed2001

Opportunities for using Navy marine mammals to explore associations between organochlorine contaminants and unfavorable effects on reproduction.

The Department of Defense (DoD) has a unique marine mammal program maintained by the US Navy that includes the largest force of bottlenose dolphins, Tursiops truncatus, worldwide. In recent years, this population of cetaceans that lives in netted open water enclosures in San Diego Bay has been monitored for levels of organochlorine (OC) contaminants in blubber, blood and milk. Data generated from these studies have afforded insight into the fate and possible effects of OC contaminants in marine mammals. We now report preliminary findings on the effects of maternal OC exposure on pregnancy outcome. Blubber OC levels were compared between females whose calves survived beyond 6 months and females whose calves were stillborn or died within 12 days of birth. The mean concentration of SigmaDDT was more than 3 times as high among dolphins whose calves died as that among dolphins whose calves survived beyond 6 months (P = 0.002). Mean SigmaPCB was more than 2.5 times higher in females whose calves did not survive (P= 0.076). This population is a logical sentinel for the assessment of environmentally mediated disease. Biological tissues and fluids can be sampled on a regular basis from the dolphins for accumulation of tissue residues, facilitated by conditioned husbandry behaviors. These trained behaviors help preclude possible alterations in health measures resulting from capture stress. Animals' diets can be monitored for contaminant levels. With these data, the expertise and facilities available at the Navy laboratory and in collaboration with other experts in the field, controlled studies can be designed to monitor and assess dietary exposure, measurable immune and neurologic responses and assess reproductive and transgenerational effects of contaminants. Biomarkers can be developed to relate the health of individual animals relative to contaminant exposures. Such investigations of natural exposure and response scenarios are a logical adjunct to traditional laboratory toxicity studies.

Adipose Tissue↗
PubMed1999

Tissue-specific induction and inactivation of cytochrome P450 catalysing lauric acid hydroxylation in the sea bass, Dicentrarchus labrax.

Microsomal cytochrome P450-dependent lauric acid hydroxylase activities were characterized in liver, kidney, and intestinal mucosa of the sea bass (Dicentrarchus labrax). Microsomes from these organs generated (omega-1)-hydroxylauric acid and a mixture of positional isomers including (omega)-, (omega-2)-, (omega-3)- and (omega-4)-hydroxylauric acids, which were identified by RP-HPLC and GC-MS analysis. Peroxisome proliferators, such as clofibrate and especially di(2-ethylhexyl) phthalate, increased kidney microsomal lauric acid hydroxylase activities. The synthesis of 11-hydroxylauric acid was enhanced 5.3-fold in kidney microsomes. Liver microsomal lauric acid hydroxylase activities were weakly affected and no significant induction was found in small intestine microsomes from clofibrate or di(2-ethylhexyl) phthalate-treated fish. The differences in lauric acid metabolisation and the tissue-specific induction by peroxisome proliferators suggest the involvement of several P450s in this reaction. Incubations of liver and kidney microsomes with lauric acid analogues (11- or 10-dodecynoic acids) resulted in a time- and concentration-dependent loss of lauric acid hydroxylase activities. The induction of these activities in fish by phthalates, which are widely-distributed environmental pollutants, may be taken into consideration for the development of new biomarkers.

Animals↗
PubMed2003

Cytology in Barrett's esophagus.

Brush cytology is complementary to endoscopic biopsy and is recommended by some to be part of the routine endoscopic surveillance of patients with BE. Advantages of cytology include the ability to sample a greater area of involved epithelium, preferential exfoliation of the less cohesive dysplastic cells, simplicity, and lower cost. There are clear cytologic criteria for dysplasia, and biomarker studies can be performed on cytologic specimens. Despite these advantages, cytology is used by only 17% of gastroenterologists in the United States today. Limited data are available on the usefulness of cytology in the diagnosis and surveillance of BE. Cytology has good sensitivity for the detection of adenocarcinoma and HGD and good specificity for the detection of IM without dysplasia. Furthermore, cytology may detect abnormalities missed by biopsy. Cytology has problems in the detection of LGD, however. For cytology to become a useful surveillance option, its sensitivity for low-grade lesions must be improved. One potential way to accomplish this is to add biomarkers to routine cytologic specimens to define patients at increased risk of progression to cancer. If simple prognostic biomarkers could be developed and validated in histology and cytologic specimens, this would provide additional support for the utility of cytologic brushings in the surveillance of BE. Cytology could then conceivably accomplish the goals of improved efficiency, risk stratification, and decreased costs in BE surveillance programs.

Adenocarcinoma↗
PubMed2005

Conservation of cancer genes in the marine invertebrate Mytilus edulis.

Mussels are susceptible to a wide range of environmental toxicants, including carcinogens, and thus are often employed as bioindicator species. To elucidate the molecular aetiology of such neoplastic damage, we have cloned Mytilus edulis homologues of the vertebrate ras proto-oncogene, and p53 tumor suppressor gene. The M. edulis ras cDNA encodes a predicted protein of 184 amino acids. The DNA sequence analysis with vertebrate ras sequences demonstrates that the M. edulis ras cDNA is highly conserved in regions of functional importance, including mutational hot spots. The partial p53 sequence also demonstrates that M. edulis p53 is highly conserved in two regions of functional importance and that these regions also include four of the five mutational hot spots for this gene. In contrast, the M. edulis p53 sequence shows little similarity to the other published invertebrate p53-like sequences. The cancer gene sequences characterized herein will allow development of specific biomarkers of genotoxic damage.

Amino Acid Sequence↗
PubMed2006

Quality control metrics for LC-MS feature detection tools demonstrated on Saccharomyces cerevisiae proteomic profiles.

Quantitative proteomic profiling using liquid chromatography-mass spectrometry is emerging as an important tool for biomarker discovery, prompting development of algorithms for high-throughput peptide feature detection in complex samples. However, neither annotated standard data sets nor quality control metrics currently exist for assessing the validity of feature detection algorithms. We propose a quality control metric, Mass Deviance, for assessing the accuracy of feature detection tools. Because the Mass Deviance metric is derived from the natural distribution of peptide masses, it is machine- and proteome-independent and enables assessment of feature detection tools in the absence of completely annotated data sets. We validate the use of Mass Deviance with a second, independent metric that is based on isotopic distributions, demonstrating that we can use Mass Deviance to identify aberrant features with high accuracy. We then demonstrate the use of independent metrics in tandem as a robust way to evaluate the performance of peptide feature detection algorithms. This work is done on complex LC-MS profiles of Saccharomyces cerevisiae which present a significant challenge to peptide feature detection algorithms.

Algorithms↗
PubMed2004

Characterization of the reaction products of 2'-deoxyguanosine and 1,2,3,4-diepoxybutane after acid hydrolysis: formation of novel guanine and pyrimidine adducts.

1,2,3,4-diepoxybutane (DEB), an important in vivo metabolite of 1,3-butadiene (BD), is a potent mutagen and a known carcinogen. Recently, DEB has been shown to react with 2'-deoxyguanosine (dG) at 37 degrees C and pH 7.4 to yield a series of nucleoside adducts, resulting from alkylation at the 7-, 1-, and N(2)-positions of dG. In addition, adducts with fused ring systems are formed. In the present study, new adducts are characterized after DEB was allowed to react with dG at pH 7.4 and the reaction mixture was then subjected to acid hydrolysis. These adducts are 7-hydroxy-6-hydroxymethyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(1H)one (H2), 2-amino-1-(4-chloro-2,3-dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H4), 2-amino-1-(2,3,4-trihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H1'/H5'), 7,8-dihydroxy-1,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one (H2'), and 5-(3,4-dihydroxy-1-pyrrolidinyl)-2,6-diamino-4(3H)pyrimidinone (H3'). The previously characterized guanine adducts, 2-amino-7-(3-chloro-2,4-dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H3) and 2-amino-7-(2,3,4-trihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H4'), were also detected. Acid hydrolysis of purified dG-DEB adducts confirmed that H2, H3/H4', H2', and H4/H1'/H5' are the hydrolysis products of N-(2-hydroxy-1-oxiranylethyl)-2'-deoxyguanosine (P4-1 and P4-2), 6-oxo-2-amino-9-(2-deoxy-beta-d-erythro-pentofuranosyl)-7-(2-hydroxy-2-oxiranylethyl)-6,9-dihydro-1H-purinium ion (P5 and P5'), 7,8-dihydroxy-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one (P6), and 1-(2-hydroxy-2-oxiranylethyl)-2'-deoxyguanosine (P8 and P9), respectively. On the other hand, the novel pyrimidine adduct H3' is formed by the decomposition of P5 and P5' during the incubation and hydrolysis. These results may facilitate the development of useful biomarkers of exposure to DEB and its precursor BD.

Biomarkers↗
PubMed2005

Reaction of 1,2,3,4-diepoxybutane with 2'-deoxyguanosine: initial products and their stabilities and decomposition patterns under physiological conditions.

1,2,3,4-Diepoxybutane (DEB), an in vivo metabolite of 1,3-butadiene (BD), is a carcinogen and a potent mutagen. Previously, DEB was shown to react with 2'-deoxyguanosine (dG) under physiological conditions to produce seven major nucleoside adducts resulting from alkylation at the N1- (P8 and P9), N7- (P5 and P5'), and both the N1- and the N2-positions of dG to form six-membered (P4-1 and P4-2) and seven-membered fused ring systems (P6), respectively [Zhang, X.-Y., and Elfarra, A. A. (2003) Chem. Res. Toxicol. 16, 1606. Zhang, X.-Y., and Elfarra, A. A. (2004) Chem. Res. Toxicol. 17, 521]. In the present study, the stabilities and decomposition products of the seven adducts under in vitro physiological conditions (phosphate buffer containing KCl, pH 7.4, 37 degrees C) were investigated. The results showed that P4-1, P4-2, and P6 were stable, whereas P5, P5', P8, and P9 were labile with half-lives of 2.6, 2.7, 16, and 16 h, respectively. P5 and P5' decomposed initially by the loss of the deoxyribose moiety to yield the corresponding guanine adduct P5D, which exhibited a half-life of 33 h and decomposed through opening of the remaining oxirane ring by dihydrogen phosphate ion, water, or chloride ion. Decomposition of P8 yielded P4-1, P6, and nucleoside products resulting from opening of the oxirane ring by dihydrogen phosphate ion, water, or chloride ion. Similarly, decomposition of P9 led to the formation of P4-2, P6, and nucleoside products resulting from opening of the oxirane ring by dihydrogen phosphate ion, water, or chloride ion. These results indicate that the initial products of the reaction of DEB with dG are P5, P5', P8, and P9, whereas P4-1, P4-2, and P6 are secondary products. The results may also facilitate development of useful biomarkers of exposure to DEB.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Synthesis and biochemical characterization of N1-, N2-, and N7-guanosine adducts of butadiene monoxide.

1,3-Butadiene is a known rodent carcinogen, but the molecular mechanisms of its carcinogenicity are poorly understood. Butadiene monoxide (BM), a known mutagenic metabolite of 1,3-butadiene, was previously shown to react with guanosine to yield two N7-guanine adducts. In the present study, eight guanosine adducts of BM were purified and characterized as diastereomeric pairs of N7-(2-hydroxy-3-buten-1-yl)guanosine (G-1 and G-3), N7-(1-hydroxy-3-buten-2-yl)guanosine (G-2 and G-5), N2-(1-hydroxy-3-buten-2-yl)guanosine (G-4 and G-7), and N1-(1-hydroxy-3-buten-2-yl)guanosine (G-6 and G-8) on the basis of stability studies and analyses by UV, 1H NMR, and fast atom bombardment mass spectrometry. While the N7-adducts exhibited half-lives of approximately 50 (G-1 and G-3) and 90 h (G-2 and G-5) upon incubation for 192 h in 100 mM phosphate buffer (pH 7.4) at 37 degrees C, the N1- and N2-adducts remained stable. When guanosine was reacted with excess BM in phosphate buffer (pH 7.4) at 37 degrees C, adduct formation exhibited pseudo-first-order kinetics, with the N7-adducts being formed approximately 10-fold more favorably than the N1- and N2-adducts. When incubations were carried out at lower BM concentrations, the N7-adducts remained the major detectable adducts, but the N2-adducts were also detectable at equimolar BM and guanosine concentrations, and the N1-adducts were detectable at a 5-fold molar excess of BM. These results, which provide clear evidence that guanosine can be alkylated at multiple sites following 1,3-butadiene exposure, may aid in the development of useful biomarkers for exposure to 1,3-butadiene. The results may also contribute to a better understanding of the molecular mechanisms of 1,3-butadiene-induced carcinogenicity.

Carcinogens↗
PubMed2003

Novel agents for chemoprevention, screening methods, and sampling issues.

An aggressive approach to breast cancer control based on preventing the disease must complement efforts at effective treatment. To date clinical trials testing new chemopreventative agents have not generally met with the kind of success expected. A wide range of new breast cancer chemopreventative agents are poised to be tested in clinical trials. We review these novel agents and approaches, including those for which clinical trials have been initiated and those that are promising in the preclinical arena. Further progress in this area requires not only new agents, but novel methods for screening for risk assessment, sampling and development of intermediate biomarkers. We review these novel potential surrogate endpoints, including new imaging-techniques, breast sampling approaches, and methods to assess biomarkers in breast epithelium. Factors that could contribute to a meaningful choice of the chemopreventive agents and the design of clinical trials are discussed.

Anticarcinogenic Agents↗
PubMed2005

The emerging role of the PI3-K-Akt pathway in prostate cancer progression.

The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.

Biomarkers, Tumor↗
PubMed2002

Tetanus antigen modulates the gene expression profile of aluminum phosphate adjuvant in spleen lymphocytes in vivo.

Adjuvants play an important role in stimulation of the immune response to antigens. Very little is known about the molecular mechanisms of this stimulation. Here we address this issue by studying gene expression profiles from spleen lymphocytes after in vivo immunization of mice with a clinically relevant vaccine, tetanus toxoid formulated with aluminum phosphate as adjuvant (TT(ADJ)), or the adjuvant alone (ADJ). The Th1/Th2 response to TT(ADJ) was obtained from a combination of up- and downstream markers to conventional cytokines, which were in good agreement with cytokine protein levels. A clustering algorithm revealed that ADJ elicited expression of 47 genes active in cytotoxic lymphocytes, inflammation, oncogenesis, stress, toxicity and cell cycle regulation. In TT(ADJ) these adjuvant-elicited genes were expressed at lower levels and a compensatory onset of protective and inhibitory genes was observed. We conclude that the antigen, to a larger extent than previously recognized, modulates the molecular mechanism of the aluminum phosphate adjuvant and that the identified genes may serve as predictive biomarkers in the development of new adjuvants and vaccines.

Adjuvants, Immunologic↗
PubMed2000

Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics.

Aberrant crypt foci (ACF) have been identified on the colonic mucosal surface of rodents treated with colon carcinogens and of humans after methylene-blue staining and observation under a light microscope. Several lines of evidence strongly suggest that ACF with certain morphological, histological, cell kinetics, and genetic features are precursor lesions of colon cancer both in rodents and in humans. Thus, ACF represent the earliest step in colorectal carcinogenesis. This paper has the main purpose of reviewing the evidence supporting this view, with particular emphasis on cell and crypt dynamics in ACF. ACF have been used as intermediate biomarkers of cancer development in animal studies aimed at the identification of colon carcinogens and chemopreventive agents. Recently, evidence has also shown that ACF can be effectively employed in chemopreventive studies also in humans.

Animals↗
PubMed2006

Neoadjuvant endocrine therapy for locally advanced breast cancer.

Patients with locally advanced breast cancer are frequently treated with preoperative (neoadjuvant) systemic therapy to downstage the tumor and improve surgical outcomes. The conventional approach has been to administer chemotherapy but for estrogen receptor-positive (ER+) tumors endocrine therapy is a logical alternative. Neoadjuvant endocrine therapy was initially investigated in older or medically frail individuals who were poor candidates for cytotoxic drugs. However, indirect comparisons suggest that preoperative endocrine therapy with an aromatase inhibitor promotes breast conservation probably as frequently as chemotherapy. As a result, primary systemic therapy with an aromatase inhibitor is now being explored in a younger, healthier population. A key advance would be the development of predictive biomarkers so that this treatment can be more confidently incorporated into routine clinical practice. Interestingly, it seems logical that such a test also would identify patients with highly endocrine therapy-responsive tumors that do not derive much benefit from adjuvant chemotherapy. The American College of Surgeons Oncology Group and the Central Clinical Trials Unit recently activated a neoadjuvant aromatase inhibitor trial with these aims in mind. In this review, we outline the rationale for preoperative endocrine therapy, and consider predictive models for endocrine therapy responsiveness in this setting.

Aged↗
PubMed2004

Vitamin C conjugates of genotoxic lipid peroxidation products: structural characterization and detection in human plasma.

alpha,beta-Unsaturated aldehydes such as 4-hydroxy-2-nonenal (HNE) and other electrophilic lipid peroxidation (LPO) products may contribute to the pathogenesis of cancer, cardiovascular diseases, and other age-related diseases by cytotoxic, genotoxic, and proinflammatory mechanisms. The notion that vitamin C (ascorbic acid) acts as a biological antioxidant has been challenged recently by an in vitro study showing that ascorbic acid promotes, rather than inhibits, the formation of genotoxic LPO products from the lipid hydroperoxide, hydroperoxy octadecadienoic acid [Lee, S. H., Oe, T. & Blair, I. A. (2001) Science 292, 2083-2086]. Here, we demonstrate that ascorbic acid acts as a nucleophile and forms Michael-type conjugates with electrophilic LPO products. Several ascorbyl-LPO product conjugates, resulting from the interaction of ascorbic acid with hydroperoxy octadecadienoic acid in vitro, were identified by tandem MS, including ascorbyl conjugates of HNE, 4-oxo-2-nonenal, and presumably, 12-oxo-9-hydroxy-10-dodecenoic acid. The same ascorbyl-LPO product conjugates were detected in human plasma. The concentration of the ascorbyl-HNE conjugate in plasma from 11 healthy subjects was found to be 1.30 +/- 0.74 microM (mean +/- SD). Our data identify ascorbylation (vitamin C conjugation) as a previously unrecognized, biologically relevant pathway for the elimination of electrophilic LPO products, and have implications for the prevention and treatment of chronic inflammatory diseases, as well as the development of novel biomarkers of oxidative stress.

Aldehydes↗
PubMed2006

The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin signaling in renal carcinoma cells.

Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion, and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. VHL loss has been shown to allow robust RCC cell motility, invasiveness, and morphogenesis in response to hepatocyte growth factor (HGF) stimulation, processes that are known to contribute to tumor invasiveness and metastatic potential. Among the most likely intracellular mediators of these HGF-driven activities is beta-catenin, a structural link between cadherens and the actin cytoskeleton, as well as a gene transactivator. We show that reconstitution of VHL expression in RCC cells repressed HGF-stimulated beta-catenin tyrosyl phosphorylation, adherens junction disruption, cytoplasmic beta-catenin accumulation, and reporter gene transactivation in RCC cells. Ectopic expression of a ubiquitination-resistant beta-catenin mutant specifically restored HGF-stimulated invasion and morphogenesis in VHL-transfected RCC cells. VHL gene silencing in non-RCC renal epithelial cells phenotypically mimicked VHL loss in RCC, and HGF-driven invasiveness was blocked by the expression of a dominant-negative mutant of Tcf. We conclude that, unlike many other cancers, where HGF pathway activation contributes to malignancy through the acquisition of autocrine signaling, receptor overexpression, or mutation, in RCC cells VHL loss enables HGF-driven oncogenic beta-catenin signaling. These findings identify beta-catenin as a potential target in biomarker and drug development for RCC.

Carcinoma, Renal Cell↗
PubMed2005

Identification of the major urinary metabolite of the highly reactive cyclopentenone isoprostane 15-A(2t)-isoprostane in vivo.

The cyclopentenone isoprostanes (A(2)/J(2)-IsoPs) are formed in significant amounts in humans and rodents esterified in tissue phospholipids. Nonetheless, they have not been detected unesterified in the free form, presumably because of their marked reactivity. A(2)/J(2)-IsoPs, similar to other electrophilic lipids such as 15-deoxy-Delta(12,14)-prostaglandin J(2) and 4-hydroxynonenal, contain a highly reactive alpha,beta-unsaturated carbonyl, which allows these compounds to react with thiol-containing biomolecules to produce a range of biological effects. We sought to identify and characterize in rats the major urinary metabolite of 15-A(2t)-IsoP, one of the most abundant A(2)-IsoPs produced in vivo, in order to develop a specific biomarker that can be used to quantify the in vivo production of these molecules. Following intravenous administration of 15-A(2t)-IsoP containing small amounts of [(3)H(4)]15-A(2t)-IsoP, 80% of the radioactivity excreted in the urine remained in aqueous solution after extraction with organic solvents, indicating the formation of a polar conjugate(s). Using high pressure liquid chromatography/mass spectrometry, the major urinary metabolite of 15-A(2t)-IsoP was determined to be the mercapturic acid sulfoxide conjugate in which the carbonyl at C9 was reduced to an alcohol. The structure was confirmed by direct comparison to a synthesized standard and via various chemical derivatizations. In addition, this metabolite was found to be formed in significant quantities in urine from rats exposed to an oxidant stress. The identification of this metabolite combined with the finding that these metabolites are produced in in vivo settings of oxidant stress makes it possible to use this method to quantify, for the first time, the in vivo production of cyclopentenone prostanoids.

Acetylcysteine↗
PubMed2005

Microarray data analysis of mouse neoplasia.

Microarray gene expression analysis offers great promise to help us understand the molecular events of experimental carcinogenesis, but have such promises been fulfilled? Studies of gene expression profiles of rodent are being published and demonstrate that yes, indeed, gene array data is furthering our understanding of tumor biology. Recent studies have identified differentially expressed genes in rodent mammary, colon, lung, and liver tumors. Although relatively few genes on the rodent arrays have been fully characterized, information has been generated to better identify signatures of histologic type and grade, understand invasion and metastasis, identify candidate biomarkers of early development, identify gene networks in carcinogenesis, understand responses to therapy, and decifer overlap with molecular events in human cancers. Data from mouse lung, mammary gland, and liver tumor studies are reviewed as examples of how to approach and interpret gene array data. Methods of gene array data analysis were also applied for discovery of genes involved in the regression of mouse liver tumors induced by chlordane, a nongenotoxic murine hepatocarcinogen. Promises are beginning to be fulfilled and it is clear that pathologists and toxicologists, in collaboration with molecular biologists, bioinformatists,and other scientists are making great strides in the design, analysis, and interpretation of microarray data for cancer studies.

Animals↗