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PubMed1993

Blood group antigens and integrins as biomarkers in head and neck cancer: is aberrant tyrosine phosphorylation the cause of altered alpha 6 beta 4 integrin expression?

Head and neck cancer is a capricious disease that varies greatly in its clinical behavior. The development of biomarkers that can distinguish between biologically aggressive and indolent tumors has been a long term goal of our laboratories. Predictive markers applicable to biopsy specimens should facilitate clinical management through early identification of patients at greatest risk for early relapse or metastatic spread. Two prominent cell surface markers that we identified by raising monoclonal antibodies to squamous cell carcinomas are blood group antigens and the A9 antigen/alpha 6 beta 4 integrin. Both of these markers are abnormally displayed in squamous cancers of the head and neck and serve as indicators of early relapse. Loss of blood group antigen expression is a stronger single indicator than is overexpression of the alpha 6 beta 4 integrin. However, use of both markers together is a stronger predictive indicator than is either alone. We know little about the function of the blood group antigens in squamous cells except that the mature antigens are associated with differentiation. Similarly, the function of the alpha 6 beta 4 integrin is also not fully understood. Integrin alpha 6 beta 4 is thought to serve as an extracellular matrix receptor, but its ligand has not been confirmed. In resting epithelium, the alpha 6 beta 4 integrin is polarized to the basal aspect of the basal cell as a component of the hemidesmosome, the anchoring structures of the epithelia. This basal polarization is lost in migrating normal squamous cells and squamous carcinomas. Tyrosine phosphorylation of the beta 4 subunit is absent or greatly reduced in malignant cells and this may be a critical signal for subcellular localization of alpha 6 beta 4 and cell anchoring. On the basis of our current experimental results, we postulate that tyrosine phosphorylation of the beta 4 subunit is a reversible signal that regulates cell migration in normal and malignant cells, and may therefore be an important initial event in the metastatic cascade.

ABO Blood-Group System↗
PubMed2006

Translating genomic biomarkers into clinically useful diagnostics.

The landmark sequencing of the human genome has ushered in a new field of large-scale research. Advances in understanding the molecular basis of disease have opened up new opportunities to develop genomics-based tools to diagnose, predict disease onset or recurrence, tailor treatment options, and assess treatment response. Although still in the early stages of research and development, genomic biomarker research has the capability of providing a comprehensive insight into pathophysiological processes as well as more precise predictors of outcome not previously attainable with traditional biomarkers. Before genomic biomarkers are incorporated into clinical practice, several issues will need to be addressed in order to generate the necessary levels of evidence to demonstrate analytical and clinical validity and utility. In addition, efforts will be needed to educate health professionals and the public about genomics-based tools, revise regulatory oversight mechanisms, and ensure privacy safeguards of the information generated from these new tests.

Biomarkers↗
PubMed1984

Genetics, biomarkers, and control of breast cancer: a review.

More has been written about the epidemiology of breast cancer than possibly any other form of cancer affecting mankind. However, in the face of this intense interest, only a paucity of attention has been given to the role of genetics in its etiology. This review represents an attempt by the investigators to provide a comprehensive coverage of hereditary breast cancer. Included are pertinent endogeneous and exogeneous risk factors, which in certain circumstances, may significantly influence the role of primary genetic factors. Hereditary breast cancer is heterogeneous. When discussing the subject, therefore, one must be precise relevant to the particular heterogeneous form of concern, based on differing tumor associations. It is probably not appropriate to discuss "hereditary breast cancer" without qualification of the specific hereditary breast cancer syndrome of concern; i.e., the SBLA syndrome, breast/ovarian cancer syndrome, and others. This reasoning also applies to attempts at linking biomarkers to hereditary breast cancer. Finally, in addition to ongoing discussions on the cardinal principles that associate with hereditary forms of breast cancer, its frequency, and new developments in biomarkers, we have provided surveillance/management programs that embrace those facets of the natural history of this disease.

Adult↗
PubMed2002

Combining several screening tests: optimality of the risk score.

The development of biomarkers for cancer screening is an active area of research. While several biomarkers exist, none is sufficiently sensitive and specific on its own for population screening. It is likely that successful screening programs will require combinations of multiple markers. We consider how to combine multiple disease markers for optimal performance of a screening program. We show that the risk score, defined as the probability of disease given data on multiple markers, is the optimal function in the sense that the receiver operating characteristic (ROC) curve is maximized at every point. Arguments draw on the Neyman-Pearson lemma. This contrasts with the corresponding optimality result of classic decision theory, which is set in a Bayesian framework and is based on minimizing an expected loss function associated with decision errors. Ours is an optimality result defined from a strictly frequentist point of view and does not rely on the notion of associating costs with misclassifications. The implication for data analysis is that binary regression methods can be used to yield appropriate relative weightings of different biomarkers, at least in large samples. We propose some modifications to standard binary regression methods for application to the disease screening problem. A flexible biologically motivated simulation model for cancer biomarkers is presented and we evaluate our methods by application to it. An application to real data concerning two ovarian cancer biomarkers is also presented. Our results are equally relevant to the more general medical diagnostic testing problem, where results of multiple tests or predictors are combined to yield a composite diagnostic test. Moreover, our methods justify the development of clinical prediction scores based on binary regression.

Bayes Theorem↗
PubMed2005

[The role of biomarkers CK7, Vim and P53 in the development of subtypes of endometrial carcinoma].

OBJECTIVE: Analyzing the protein expression of biomarkers CK7, Vim, and P53 to investigate their possible pathogenic roles in the development of variant subtypes of endometrial carcinoma. METHODS: Biomarkers CK7, Vim, and P53 were immunohistochemistry-stained among 131 endometrial carcinoma specimens including 93 endometroid, 8 adenoacanthoma, and 32 rare subtypes of adenosquamas carcinoma, clean cell carcinoma, and papillary carcinoma, which had been confirmed clinically and pathologically, and studied statistically with Fisher test and Cochran-Mantel-Haenszel (CMH) Test. RESULTS: Positive correlation was demonstrated among CK7, Vim, and P53 expression levels. The CK7 protein expression is increased, while the Vim and P53 are decreased in the subtype of endometrioid carcinoma. The clinical staging of endometriroid carcinoma is positively correlated with the expression of Vim. The positive rate of Vim and P53 is correlated with cytological differentiation of the carcinoma cells. CONCLUSION: Biomarkers CK7, Vim, and P53 are playing pathogenic roles, assuming as a mutual transcriptional modulator, and Vim but not P53 is likely the favorable prognostic factor, in the development of variant subtypes of endometrial carcinoma in addition to a evaluating the treatment.

Adult↗
PubMed2005

Real-time QCM-D immunoassay through oriented antibody immobilization using cross-linked hydrogel biointerfaces.

This report presents the development of pre-cross-linked and in situ cross-linked polyethyleneimine-carboxymethylcellulose antibody immobilization platforms for real-time QCM-D immunoassay of sepsis-related biomarkers. These platforms differ significantly from recent trends in QCM-based assays, a rapidly expanding field given the affordability and sensitivity of the transduction system, by providing ultrafast biointerface deposition through cross-linking of polysaccharides. Using rhIL-1ra (17 kDa), a known sepsis biomarker, for development, various immunoassay modifications to increase sensitivity were investigated, including the use of Protein A, Protein G, and anti-IgG Fc specific antibody capture ligands for oriented antibody immobilization, higher-frequency QCM-D crystals, and amplification using secondary antibodies. The optimized assay employs Protein A oriented immobilization on pre-cross-linked polymer and secondary antibodies to achieve a detection limit of 25 ng/mL on 5 MHz crystals. Assay repeatability using the optimized chemistry is robust, with no loss in 100 ng/mL antigen detection over 20 cycles of the 10 min sandwich assay. Nonspecific adsorption of human serum albumin, as characterized by ToF-SIMS, is minimal and negligible for the pre-cross-linked and in situ cross-linked compositions, respectively.

Antibodies↗
PubMedDate not supplied

Chemoprevention for high-risk women: tamoxifen and beyond.

The demonstration by the National Surgical Adjuvant Breast Project (NSABP) that 5 years of tamoxifen therapy is associated with an approximate 50% reduction in breast cancer incidence in high-risk women was a milestone in breast cancer prevention. Because tamoxifen is associated with increased risk of side-effects such as hot flashes, menstrual abnormalities, uterine cancer, and thromboembolic phenomena, its use will not be advisable or acceptable for all high-risk women. Women over 50 years of age appear to be at highest risk for serious adverse events, such as uterine cancer and thromboembolic phenomena. Individuals in whom tamoxifen-associated breast cancer risk reduction appears to outweigh risk of serious side-effects include women with prior in situ or estrogen receptor (ER)-positive invasive cancer, atypical hyperplasia, and/or women ages 35-49 with a calculated Gail 5-year risk of > or =1.7%, hysterectomized women aged 50 and older with a 5-year Gail risk of > or =2.5%, and nonhysterectomized women aged 50 and older with a 5-year Gail risk of >5.0%. It is not yet clear whether tamoxifen can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation. Raloxifene is a selective ER modulator with less uterine estrogen agonist activity than tamoxifen, and it is hoped that it will result in fewer uterine cancers but will be equally efficacious in reducing the risk of breast cancer. The NSABP is currently conducting a randomized study of tamoxifen versus raloxifene in high-risk postmenopausal women. Approximately one third of invasive cancers are ER negative. Tamoxifen does not reduce the incidence of ER-negative cancers, nor does it appear to be effective in preventing the appearance of one third of ER-positive cancers. Priorities in prevention research are to develop (a) biomarkers to refine short-term risk assessments based on epidemiologic models, (b) biomarkers predictive of response to specific classes of preventive agents, (c) drugs with fewer side-effects and/or effective in ER-negative or ER-positive tamoxifen-resistant precancerous disease, and (d) efficient clinical trial models to assess new agent efficacy. Breast intraepithelial neoplasia (IEN) may be sampled by minimally invasive techniques and is an attractive short-term risk biomarker. Molecular abnormalities observed in IEN may be used to select potential agents for testing/therapy, and modulation of these abnormalities may be used in phase I trials to select appropriate doses and in phase II trials to assess response. Breast density volume and certain serum markers such as insulin-like growth factor-1 are also being studied as potential risk and response biomarkers. Reversal or prevention of advanced IEN as well as modulation of other risk biomarkers in randomized phase II and phase III trials is being evaluated as a means of more efficiently evaluating prevention drugs in the future. A number of agents are being developed that target molecular abnormalities in IEN, have fewer or different side effects than tamoxifen, and may be effective in ER-negative or tamoxifen-resistant disease.

Breast Neoplasms↗
PubMed1994

Application of reliability models to studies of biomarker validation.

We present a model of biomarker validation developed in our laboratory, the results of the validation study, and the impact of the estimation of the variance components on the design of future molecular epidemiologic studies. Four different biomarkers of exposure are illustrated: DNA-protein cross-link (DNA-PC), DNA-amino acid cross link (DNA-AA), metallothionein gene expression (MT), and autoantibodies to oxidized DNA bases (DNAox). The general scheme for the validation experiments involves n subjects measured on k occasions, with j replicate samples analyzed on each occasion. Multiple subjects, occasions, and replicates provide information on intersubject, intrasubject, and analytical measurement variability, respectively. The analysis of variance showed a significant effect of batch variability for DNA-PC and MT gene expression, whereas DNAox showed a significant between-subject variability. Among the amino acids tested, cysteine and methionine showed a significant contribution of both batch and between-subject variability, threonine showed between-subject variability only, and tyrosine showed between-batch and between-subject variability. The total variance estimated through the experiment was used to calculate the minimum sample size required for a future epidemiologic study including the same biomarkers used for the reliability study. Such validation studies can detect the various components of variability of a biomarker and indicate needed improvements of the assay, along with possible use in field studies.

Amino Acids↗
PubMed2003

What is the relevance of bioinformatics to pharmacology?

Although bioinformatics achieved prominence because of its central role in genome data storage, management and analysis, its focus has shifted as the life sciences exploit these data. In pharmacology, genomic, transcriptomic and proteomic data are being used in the quest for drugs that fulfill unmet medical needs, are disease modifying or curative and are more effective and safer than current drugs. Bioinformatics is used in drug target identification and validation and in the development of biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic benefit of drugs. Now that the 'parts list' of cellular signalling pathways is available, integrated computational and experimental programmes are being developed, with the goal of enabling in silico pharmacology by linking the genome, transcriptome and proteome to cellular pathophysiology.

Computational Biology↗
PubMed2004

Recent developments in the determination of urinary cancer biomarkers by capillary electrophoresis.

Investigation of effective biomarkers for cancers is currently a popular area of study in clinical and cancer researches, because it can potentially lead to pre-cancer screening or pre-cancer diagnosis and may provide useful information on cancer type and the disease's stage of progression. More and more biochemical or chemical fluid components of the human body such as urine, blood, and cerebrospinal fluid have been considered to contain biomarkers, which are useful in cancer researches, pre-cancer diagnosis, and cancer follow-ups during or after cancer treatment. Several modern analytical techniques, such as gas chromatography (GC), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and other separation techniques as well as hyphenated techniques, have been extensively used in study of cancer biomarkers. Among these techniques, CE is considered to be a highly efficient and practical analytical technique because of the small sample volume requirement and its wide separation versatility, ranging from small inorganic molecules to large biomolecules. This review discusses the latest developments involving biomarkers and their analysis by CE, including a discussion of instrumental conditions, method developments, and data analysis.

Biomarkers, Tumor↗
PubMed2000

Current concepts in biomarker technology for bladder cancers.

BACKGROUND: Transitional cell carcinoma of the bladder (TCC) is the second most common malignancy of the urinary tract. More than 70% of treated tumors recur, and 30% of recurrent tumors progress. Currently, pathologic staging and grading are valuable prognostic factors for detecting and monitoring TCC. Urinalysis, cystoscopy, and cytology are either invasive or lack sensitivity and specificity. The availability of a noninvasive, reliable, and simple test would greatly improve the detection and monitoring of patients with TCC. Several biomarkers for bladder cancer have been proposed, but no single marker has emerged as the test of choice. APPROACH: We undertook a comprehensive literature search using Medline to identify all publications from 1980 to 1999. Articles that discussed potential biomarkers for TCC were screened. Only compounds that demonstrated high sensitivity or specificity, significant correlation with TCC diagnosis and staging, and extensive investigation were included in this review. CONTENT: Potential biomarkers of disease progression and prognosis include nuclear matrix protein, fibrin/fibrinogen product, bladder tumor antigen, blood group-related antigens, tumor-associated antigens, proliferating antigens, oncogenes, growth factors, cell adhesion molecules, and cell cycle regulatory proteins. The properties of the biomarkers and the methods for detecting or quantifying them are presented. Their sensitivities and specificities for detecting and monitoring disease were 54-100% and 61-97%, respectively, compared with 20-40% and 90% for urinalysis and cytology. SUMMARY: Although urine cytology and cystoscopy are still the standard of practice, many candidate biomarkers for TCC are emerging and being adopted into clinical practice. Further research and better understanding of the biology of bladder cancer, improved diagnostic techniques, and standardized interpretation are essential steps to develop reliable biomarkers. It is possible that using the current biomarkers as an adjuvant modality will improve our ability to diagnose and monitor bladder cancer.

Biomarkers, Tumor↗
PubMed2005

Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars.

The Mars Organic Analyzer (MOA), a microfabricated capillary electrophoresis (CE) instrument for sensitive amino acid biomarker analysis, has been developed and evaluated. The microdevice consists of a four-wafer sandwich combining glass CE separation channels, microfabricated pneumatic membrane valves and pumps, and a nanoliter fluidic network. The portable MOA instrument integrates high voltage CE power supplies, pneumatic controls, and fluorescence detection optics necessary for field operation. The amino acid concentration sensitivities range from micromolar to 0.1 nM, corresponding to part-per-trillion sensitivity. The MOA was first used in the lab to analyze soil extracts from the Atacama Desert, Chile, detecting amino acids ranging from 10-600 parts per billion. Field tests of the MOA in the Panoche Valley, CA, successfully detected amino acids at 70 parts per trillion to 100 parts per billion in jarosite, a sulfate-rich mineral associated with liquid water that was recently detected on Mars. These results demonstrate the feasibility of using the MOA to perform sensitive in situ amino acid biomarker analysis on soil samples representative of a Mars-like environment.

Amino Acids↗
PubMed2006

[What are the etiological medical therapies in amyotrophic lateral sclerosis?].

The increasing knowledge about Amyotrophic Lateral sclerosis (ALS) led to the development of the first and only available treatment: riluzole. The efficacy of this drug has been demonstrated in two controlled clinical trials. The data showed that riluzole increases the rates of survival in patients suffering from ALS. This increase was about 25 percent over a period of 12 months of treatment. Since its marketing, the clinical efficacy of riluzole was confirmed in several epidemiological studies. Tested initially because of its anti-glutamates qualities, the exact mechanisms of action responsible for the efficacy of Riluzole in ALS remains unknown. Furthermore, despite a strong rational based on important literature, several other anti-glutamates drugs failed to demonstrate efficacy in ALS, nor did numerous anti-oxydant, neurotrophics, immunomodulators, and favoring mitochondrial metabolism drugs. Despite the low rate of patients showing an increase of liver enzymes, a strict control of liver functions is necessary with a treatment by riluzole. its dose should be increased gradually in case of important fatigue, a change of the general state, or respiratory incapacity. Because of the neuroprotectrives qualities of riluzole, early neuronal death in ALS, the difficulty to confirm early the diagnosis, and the evident interest to treat in the first stage, the treatment of the suspected forms of the disease becomes justifiable. The perspectives of treatment of ALS will depend on our capacity to understand better the physiopathology, the reasons of failures in the past, and to develop new biomarkers. They will depend also on our capacity to include in clinical trials and to follow up over a long time, an important number of patients. Different new methods, as the cellular therapy are in development, and represent a real hope for the future.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Endocrine disruptors in marine organisms: approaches and perspectives.

Organic pollutants exhibiting endocrine disrupting activity (Endocrine Disruptors--EDs) are prevalent over a wide range in the aquatic ecosystems; most EDs are resistant to environmental degradation and are considered ubiquitous contaminants. The actual potency of EDs is low compared to that of natural hormones, but environmental concentrations may still be sufficiently high to produce detrimental biological effects. Most information on the biological effects and mechanisms of action of EDs has been focused on vertebrates. Here we summarize recent progress in studies on selected aspects of endocrine disruption in marine organisms that are still poorly understood and that certainly deserve further research in the near future. This review, divided in four sections, focuses mainly on invertebrates (effects of EDs and mechanisms of action) and presents data on top predators (large pelagic fish and cetaceans), a group of vertebrates that are particularly at risk due to their position in the food chain. The first section deals with basic pathways of steroid biosynthesis and metabolism as a target for endocrine disruption in invertebrates. In the second section, data on the effects and alternative mechanisms of action of estrogenic compounds in mussel immunocytes are presented, addressing to the importance of investigating full range responses to estrogenic chemicals in ecologically relevant invertebrate species. In the third section we review the potential use of vitellogenin (Vtg)-like proteins as a biomarker of endocrine disruption in marine bivalve molluscs, used worldwide as sentinels in marine biomonitoring programmes. Finally, we summarize the results of a recent survey on ED accumulation and effects on marine fish and mammals, utilizing both classical biomarkers of endocrine disruption in vertebrates and non-lethal techniques, such as non-destructive biomarkers, indicating the toxicological risk for top predator species in the Mediterranean. Overall, the reviewed data underline the potential to identify specific types of responses to specific groups of chemicals such as EDs in order to develop suitable biomarkers that could be useful as diagnostic tools for endocrine disruption in marine invertebrates and vertebrates.

Animals↗
PubMed2005

Retinoid receptor mRNA expression profiles in human bladder cancer specimens.

Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 target genes, DAB2 and Midkine, in normal and malignant bladder tissue specimens from human patients. We evaluated 24 normal and malignant bladder specimens for retinoid receptor, DAB2 and Midkine mRNA expression using RT-PCR. We also examined the effects of retinoic acid and retinol on the expression of these genes in five human bladder cancer cell lines. Expression of RARalpha, RARbeta2, RARgamma and RXRalpha mRNA was detected in all of the non-neoplastic patient bladder specimens. RARbeta2 mRNA expression was undetectable in 7/13 tumors, RARalpha in 3/13, RARgamma in 1/13 and RXRalpha in 2/13. DAB2 mRNA was expressed in all non-neoplastic and all tumor specimens, while Midkine mRNA was detected in 8/11 non-neoplastic specimens versus 11/13 tumors. Two of the five bladder cancer cell lines expressed RARbeta2 independent of retinoid exposure; in three cell lines RARbeta2 expression was induced by retinoids. RARalpha, RARgamma and RXRalpha mRNA expression was detected in 5/5 cell lines, independent of retinoid exposure. We found a reduction in retinoid receptor mRNA expression, particularly for RARbeta2, in human bladder cancer specimens. We also demonstrated induction of RARbeta2 mRNA expression in some of the retinoid-treated bladder cancer cell lines. We suggest that restoration of RARbeta2 expression may be a reasonable biomarker for developing bladder cancer preventive and/or therapeutic drugs.

Aged↗
PubMed2004

Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers.

CONTEXT: Intra-amniotic infection (IAI) is commonly associated with preterm birth and adverse neonatal sequelae. Early diagnosis of IAI, however, has been hindered by insensitive or nonspecific tests. OBJECTIVE: To identify unique protein signatures in rhesus monkeys with experimental IAI, a proteomics-based analysis of amniotic fluid was used to develop diagnostic biomarkers for subclinical IAI in amniotic fluid and blood of women with preterm labor. DESIGN, SETTING, AND PARTICIPANTS: Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry, gel electrophoresis, and tandem mass spectrometry were used to characterize amniotic fluid peptides in 19 chronically instrumented pregnant rhesus monkeys before and after experimental IAI. Candidate biomarkers were determined by liquid chromatography-tandem mass spectrometry. Polyclonal antibodies were generated from synthetic peptides for validation of biomarkers of IAI. Amniotic fluid peptide profiles identified in experimental IAI were subsequently tested in a cohort of 33 women admitted to Seattle, Wash, hospitals between June 25, 1991, and June 30, 1997, with preterm delivery at 35 weeks or earlier associated with subclinical IAI (n = 11), preterm delivery at 35 weeks or earlier without IAI (n = 11), and preterm contractions with subsequent term delivery at later than 35 weeks (n = 11). MAIN OUTCOME MEASURES: Identification of peptide biomarkers for occult IAI. RESULTS: Protein expression profiles in amniotic fluid showed unique signatures of overexpression of polypeptides in the 3- to 5-kDa and 10- to 12-kDa molecular weight ranges in all animals after infection and in no animal prior to infection. In women, the 10- to 12-kDa signature was identified in all 11 patients with subclinical IAI, in 2 of 11 with preterm delivery without IAI, and in 0 of 11 with preterm labor and term delivery without infection (P<.001). Peptide fragment analysis of the diagnostic peak in amniotic fluid identified calgranulin B and a unique fragment of insulinlike growth factor binding protein 1, which were also expressed in maternal serum. Mapping of other amniotic fluid proteins differentially expressed in IAI identified several immunoregulators not previously described in amniotic fluid. CONCLUSIONS: This proteomics-based characterization of the differential expression of amniotic fluid proteins in IAI identified a distinct proteomic profile in an experimental primate chorioamnionitis model that detected subclinical IAI in a human cohort with preterm labor. These diagnostic protein expression signatures, complemented by immunodetection of specific biomarkers in amniotic fluid and in maternal serum, might have application in the early detection of IAI.

Adult↗
PubMed2006

The trajectory of biomarkers in symptom management for older adults with cancer.

OBJECTIVES: To provide an overview of the trajectory of select biomarkers and their potential usefulness in symptom management in the older individual with cancer. DATA SOURCES: Empirical data and literature review. CONCLUSION: Biomarkers offer significant opportunities to understand the biological impact of cancer and its treatment on older adults whose response is likely different from their younger counterparts. Large well-designed multi-site clinical trials with adequate numbers and power are necessary to create evidenced-based practice changes. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to understand the science and implications of biomarkers to develop interventions in response to the mechanisms of symptoms experienced by older adults with cancer.

Adrenal Cortex↗
PubMedDate not supplied

Development of symbiosis-specific genes as biomarkers for the early detection of cnidarian-algal symbiosis breakdown.

Coral bleaching, i.e. the loss of dinoflagellate symbionts from cnidarian hosts, is occurring globally at increasing rates, scales, and severity. The significance of these bleaching events to the health of coral reef ecosystems is extreme, as bleached corals exhibit high mortality, reduced fecundity and productivity and increased susceptibility to disease. This decreased coral fitness leads to reef degradation and ultimately to the breakdown of the coral reef ecosystem. To date there has been little work describing the application of biomarkers to assess coral health. The most commonly applied biomarker is, in fact, the bleaching event itself. We are interested in developing early warning biomarkers that can detect coral stress before bleaching occurs. Recently, several genes that are likely to function in regulating interactions between cnidarians and their symbionts have been characterized, using the temperate sea anemone Anthopleura elegantissima as a model species. One "symbiosis gene" identified from the host genome, sym32, is expressed as a function of anemone symbiotic-state, where sym32 expression is higher in symbiotic cf. aposymbiotic (symbiont-free) anemones. Real-time quantitative RT-PCR suggested that the level of sym32 expression was correlated with the abundance of algae in the host. Furthermore, laboratory exposures of anemones to low levels of cadmium (0, 20, 100 microg(-1) CdCl2; 14 days), which caused no change in algal cell numbers, resulted in a down-regulation of sym32 compared to controls, indicating that sym32 expression may serve as a new sensitive early warning biomarker of cnidarian-algal symbiosis breakdown.

Animals↗