Special Issue "Biomarkers 2011"
Quicklinks
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Diagnostics".
Deadline for manuscript submissions: closed (31 July 2011)
Special Issue Editor
Guest Editor
Prof. Dr. Robert Bowser
Barrow Neurological Institute & St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA
Website: http://path.upmc.edu/cmp/fac05.htm
E-Mail: bowserrp@upmc.edu
Phone: +1 602 406 8989
Fax: +1 602 406 6459
Special Issue Information
Dear Colleagues,
The expanding field of biomarkers continues to play important roles in the healthcare industry, basics sciences, and the pharmaceutical industry. Biomarkers are changing the way in which we diagnose and classify disease, as well as providing a means to monitor disease progression or the effects of therapy. In addition, biomarkers are providing new insights into mechanisms of disease and new therapeutic targets. Biomarkers may be any quantitative measure of cellular, biochemical, or genetic alteration that occurs in a physiologic condition. While genomic and proteomic biomarkers have been at the forefront for the past number of years, recent technologic advancements have enabled the development of additional metabolic and peptide based biomarkers to the study of disease states. However it is crucial to demonstrate clinical validation of the biomarker before determining the clinical utility of any biomarker or panel of biomarkers. This special issue on biomarkers for the International Journal of Molecular Sciences will highlight recent advancements in biomarker discovery efforts and their clinical utility.
Prof. Dr. Robert Bowser
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).
Keywords
- proteomics
- genomics
- metabolomics
- peptidomics
- mass spectrometry
- bioinformatics
- microarray
- 2D gel electrophoresis
Published Papers (10 papers)
|
Received: 30 March 2011; in revised form: 17 May 2011 / Accepted: 24 May 2011 / Published: 1 June 2011
Show/Hide Abstract
| Download PDF Full-text (497 KB) | Download XML Full-text
Abstract: The aim of study is to identify cisplatin-resistance associated biomarkers for non-small cell lung cancers (NSCLC). We use two-dimensional electrophoresis (2-DE) combined with MALDI-TOF mass spectrometry to compare the proteome between lung cancer cell line A549 and its cisplatin-resistant subline A549/DDP. Nine cisplatin resistance-related proteins were identified, and DJ-1, one of the differently expressed proteins, was selected for further validation and evaluation. Immunohistochemical results demonstrated that high expression level of DJ-1 was associated with cisplatin resistance and a predictor for poor prognosis in 67 locally advanced NSCLC patients. Furthermore, in vitro results showed that silencing DJ-1 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, DJ-1 might play an important role in the resistibility to cisplatin, and it could also act as a novel candidate biomarker for predicting the response of NSCLC patients to cisplatin-based chemotherapy.
|
|
Received: 28 April 2011; in revised form: 27 June 2011 / Accepted: 4 July 2011 / Published: 13 July 2011
Show/Hide Abstract
| Download PDF Full-text (230 KB) | Download XML Full-text
Abstract: Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER), progesterone receptor (PR), and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.
|
|
Received: 28 June 2011; in revised form: 21 July 2011 / Accepted: 27 July 2011 / Published: 3 August 2011
Show/Hide Abstract
| Download PDF Full-text (462 KB) | Download XML Full-text
Abstract: This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4), a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC) and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3%) expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010). In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.
|
|
Received: 13 July 2011; in revised form: 16 August 2011 / Accepted: 31 August 2011 / Published: 5 September 2011
Show/Hide Abstract
| Download PDF Full-text (318 KB) | Download XML Full-text
Abstract: Abnormalities of chromosome 17 are important molecular genetic events in human breast cancers. Several famous oncogenes (HER2, TOP2A and TAU), tumor suppressor genes (p53, BRCA1 and HIC-1) or DNA double-strand break repair gene (RDM1) are located on chromosome 17. We searched the literature on HER2, TOP2A, TAU, RDM1, p53, BRCA1 and HIC-1 on the Pubmed database. The association of genes with chromosome 17, biological functions and potential significance are reviewed. In breast cancer, the polysomy 17 (three or more) is the predominant numerical aberration. HER2 amplification is widely utilized as molecular markers for trastuzumab target treatment. Amplified TOP2A, TAU and RDM1 genes are related to a significant response to anthracycline-based chemotherapy, taxane or cisplatin, respectively. In contrast, p53, BRCA1 and HIC-1 are important tumor suppressor genes related to breast carcinogenesis. This review focused on several crucial molecular markers residing on chromosome 17. The authors consider the somatic aberrations of chromosome 17 and associated genes in breast cancer.
 |
|
Received: 5 July 2011; in revised form: 17 August 2011 / Accepted: 22 August 2011 / Published: 5 September 2011
Show/Hide Abstract
| Download PDF Full-text (381 KB) | Download XML Full-text
Abstract: Primary vitreoretinal lymphoma (PVRL) or primary intraocular lymphoma, a subtype of primary central nervous system lymphoma, often masquerades as uveitis. The diagnosis of PVRL requires identification of lymphoma cells inside the eye, which is often challenging due to the frequent necrosis and admixing of PVRL cells with reactive lymphocytes. Therefore, detection of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements provide molecular diagnosis of B- and T-cell lymphoma, respectively. We retrospectively evaluated 208 cases with a clinical diagnosis of masquerade syndrome from 1998 to 2010. In 200 cases with molecular analyses using microdissection and polymerase chain reaction, we found that 110 cases had IgH gene rearrangement, 5 cases had TCR gene rearrangement, and 85 cases were negative for these two gene arrangements. The molecular data corroborated the cytopathological diagnoses of PVRL and uveitis in the majority of cases. Cytokine above the detected levels in the specimens were also measured in 80 of the 208 cases. A ratio of vitreous IL-10 to IL-6 greater than 1, suggesting PVRL, was found in 56/80 cases; 53/56 had the correct diagnosis. A ratio less than 1, suggesting uveitis, was found in 24/80 cases; 17/24 correctly confirmed the diagnosis. Moreover, the molecular data corresponded well with the clinical course of the diseases. The sensitivity and specificity of these molecular biomarkers for the diagnosis of PVRL are higher than 95%.
|
|
Received: 5 August 2011; in revised form: 30 August 2011 / Accepted: 8 September 2011 / Published: 14 September 2011
Show/Hide Abstract
| Download PDF Full-text (182 KB) | Download XML Full-text
Abstract: The incidence and mortality of pancreas cancer converge. There has been little advancement in the treatment of pancreas cancer since the acceptance of gemcitabine as the standard therapy. Unfortunately, the efficacy of gemcitabine is dismal. While there is much discussion for the development of biomarkers to help direct therapy in this area, there is little action to move them into clinical practice. Herein, we review potential pancreatic cancer biomarkers and discuss the limitations in their implementation.
|
|
Received: 24 August 2011; in revised form: 16 September 2011 / Accepted: 20 September 2011 / Published: 23 September 2011
Show/Hide Abstract
| Download PDF Full-text (314 KB) | Download XML Full-text
Abstract: Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias.
|
|
Received: 15 August 2011 / Accepted: 9 October 2011 / Published: 21 October 2011
Show/Hide Abstract
| Download PDF Full-text (261 KB) | Download XML Full-text
Abstract: Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies.
|
|
Received: 3 August 2011; in revised form: 11 October 2011 / Accepted: 7 November 2011 / Published: 16 November 2011
Show/Hide Abstract
| Download PDF Full-text (179 KB) | Download XML Full-text
Abstract: Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disorder of the central nervous system (CNS). Although many advances have been made in the comprehension of its pathogenesis, the etiology is still unknown. The complexity of MS reflects in the extreme variability of the clinical manifestations and clinical course both between and within patients, in addition to immunopathological mechanisms and response to treatment. Several prognostic factors have been suggested in large scale studies, but predictions in individual cases are difficult to make. Cerebrospinal fluid (CSF) biomarkers, such as 14-3-3, tau, and cystatin C are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, none has shown sufficient reproducibility to be applied in clinical practice. Here we review the current literature addressing the above mentioned biomarkers as MS severity predictors at an early stage.
|
|
Received: 13 September 2011; in revised form: 28 October 2011 / Accepted: 12 December 2011 / Published: 20 December 2011
Show/Hide Abstract
| Download PDF Full-text (236 KB) | Download XML Full-text
Abstract: Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.
|
Planned Papers
The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Last update: 26 September 2012
