**12. References**

Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350-5.


1. Selection of miRNAs as biomarkers for

2. Measuring miRNAs (microarray and real

3. Verification of miRNAs as biomarkers in

5. Validation of miRNAs as biomarkers for

Fig. 6. Key steps for validation of miRNAs as suitable biomarkers of oxidative stress

4. Test the sensitivity, simplicity, and specificity of miRNAs for oxidative stress-induced

oxidative stress using antioxidants (oats)

In last two decades, there has been great progress in development of biomarkers of oxidative stress that may eventually be useful in disease prevention. The challenges for future miRNA studies are (1) to validate available biomarkers for oxidative stress in animal and human studies based on their specificity, stability for storage, reproducibility, causal relation with disease, and response to antioxidant intervention; (2) to examine the basal lebels of oxidative damage in healthy subjects; and (3) to assess the long-term effect of antioxidants, such as oats, on oxidative damage by well-designed, randomized, controlled trials in human and as well as to examine the consistency of the findings among various studies. The identification of miRNAs as biomarkers of oxidative damage, if validated, may open the way for the development of early detection and prevention strategies for oxidative

This work was supported by National Institute of Health grants AA18729 (Y.T.), AA019405 (A.K.) and AA020216 (A.K.), and in part by mentoring program of Department of Internal

Babar IA, Slack FJ, Weidhaas JB (2008) miRNA modulation of the cellular stress response.

Banan A, Choudhary S, Zhang Y, Fields JZ, Keshavarzian A (2000a) Oxidant-induced

intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med

Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350-5.

suitable animal model (ALD)

oxidative stress

time PCR)

injury

**10. Future direction** 

stress-associated human diseases.

Medicine of Rush University Medical Center (Y.T.).

Future Oncol 4(2):289-98.

28(5):727-38.

**11. Acknowledgement** 

**12. References**


**16** 

*1UK 2Greece* 

**The Discovery of Cancer Tissue** 

**Case Studies on Prostate Cancer** 

*2Biomedical Research Foundation, Academy of Athens, Athens,* 

*1Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton,* 

Carcinogenesis remains a complex and unpredictable process that involves defects in multiple signalling pathways. Environmental determinants and lifestyle practices may contribute toward their onset by the exposure to a variety of carcinogenic agents. Since the process of carcinogenesis involves the **synergistic induction** in multiple pathways inside the cell, an effective means to investigate and understand them is to engage a global approach that identifies and considers multiple changes simultaneously at the protein level (Albini & Sporn, 2007; Alderton, 2007; Hanahan & Weinberg, 2011; Mueller & Fusenig, 2004). Such an approach can be effectively engaged with the use of discovery proteomics that allows for the large-scale analysis of protein identity and expression (Anderson, Anderson, et al., 2009; Cox & Mann, 2011; Cravatt, Simon, & Yates, 2007; Diamandis, 2004; Nilsson et al., 2010; Walther & Mann, 2010; Wright, Han, & Aebersold, 2005). There is increasing strong evidence that tumorigenesis occurs in the **tissue microenvironment** as a whole, involving the active crosstalk between epithelial, endothelial, immune and stromal cells (Albini &Sporn, 2007; Alderton, 2007; Mueller & Fusenig, 2004). Consequently, the analysis at the whole tissue level is a logical initial step in the identification of tissue-specific or tissueprevalent proteins occurring at larger concentration levels relative to those found in the systemic circulation, wherein their secretion and shedding may occur (Hanash, Pitteri, & Faca, 2008). Provided that the expressed tissue specific and prevalent proteins found in the serum or plasma represent phenotypic cancer pathophysiological events, then these proteins may be potential cancer biomarkers and/or physiologic treatment targets (Hanash, Pitteri, &

Research involving the mass spectrometry (MS) based proteomic study of fresh-frozen whole prostate tissue biopsies, cell-culture models and blood sera originating from welldefined clinical designs are discussed. Emphasis is given to those approaches involving the hyphenation of liquid chromatography with mass spectrometry by means of electrospray

**1. Introduction** 

Faca, 2008).

Corresponding Authors

 \*

**Specific Proteins in Serum:** 

Spiros D. Garbis1,2,\* and Paul A. Townsend1,\*

Tang Y, Forsyth CB, Farhadi A, Rangan J, Jakate S, Shaikh M, Banan A, Fields JZ, Keshavarzian A (2009c) Nitric Oxide-Mediated Intestinal Injury Is Required for Alcohol-Induced Gut Leakiness and Liver Damage. Alcohol Clin Exp Res.
