E disease condition [27,31?3]. Furthermore, in neuroendocrine or small cell prostate cancer

E disease condition [27,31?3]. Furthermore, in neuroendocrine or small cell prostate cancer, very little or no PSA is produced, and therefore PSA changes do not correlate with disease status [33]. Thomson et al. [34] reported that CaP can be detected in approximately 15 of men with normal or low levels of total PSA level. This data questions the validity of PSA as a global serum-biomarker for men. Our study in this context is significant as we provide evidence that BMI1 could be a reliable predictive secretory biomarker for both the races especially African-American CaP. This is evident from our data we show that E006 cell (derived from African American CaP patient) does not express PSA [14], however secrete BMI1 in culture media (Fig. 2D). Notably, E006 cell line also expressed intracellular BMI1 (Fig. 2B). This data Title Loaded From File suggest that BMI1 could be used as a biomarker for even those cases in African-American men who exhibit very low PSA levels but develop CaP disease. This corroborates to our data in Caucasian men, where we were able to detect BMI1 in patients which exhibited very low PSA levels (Table 2). Furthermore, BMI was found to independent of androgen and thus, it may be very useful as a prognostic biomarker in patients with both early as well as advanced prostate cancer. Thus, analysis of BMI1 in tissue biopsies and serum analysis may serve as a prognostic biomarker in CaP and may ultimately lead to monitoring therapeutic response during CaP treatment protocols. We suggest that BMI1 stands out as a promising molecule to be Title Loaded From File developed as an ideal serum-biomarker forBMI1:Potential Serum-Biomarker for Prostate Cancerprognosis of CaP in humans. We suggest that this study has high translational potential however, warrants further investigation in a big cohort of human patients. It is imperative that BMI1 as a biomarker be studied rigorously in parallel with drug development (which is underway in our laboratory), given the potential to maximize benefit and management of CaP disease in Caucasian as well as African-American patients, that in turn will minimize the harms and costs to society.Author ContributionsConceived and designed the experiments: MS. Performed the experiments: HRS AP WZ EJB. Analyzed the data: HRS RJK BRK EJB MS. Contributed reagents/materials/analysis tools: MS SK JSR. Wrote the paper: HRS.
Nucleic acids are highly polymorphic: depending on the sequences and environmental conditions they may exist in a variety of secondary structures such as duplexes, triplexes, tetraplexes, bulges, hairpins, loops [1,2]. Such non-canonical structures in nucleic acids are of general biological significance: they have been postulated to mediate protein-nucleic acid interactions, either by contacting protein residues directly or by producing a distinct tertiary structure 1527786 to which the protein binds [3], and to function as intermediates in the generation of frameshift mutations when errors in DNA replication occur [4,5]. In particular, extra-helical bases are thought to be implicated in nucleic acid non-canonical functions [6]. An essentially unlimited combination of secondary structural elements has been extensively described in RNA, where the single-stranded (ss) nucleic acid folds back on itself; however, DNA can also produce complex secondary structures during replication and recombination [7]. A shift of the reading frame during template-dependent DNA synthesis can lead to the addition or deletion of one or more nucleotide residues (nt.E disease condition [27,31?3]. Furthermore, in neuroendocrine or small cell prostate cancer, very little or no PSA is produced, and therefore PSA changes do not correlate with disease status [33]. Thomson et al. [34] reported that CaP can be detected in approximately 15 of men with normal or low levels of total PSA level. This data questions the validity of PSA as a global serum-biomarker for men. Our study in this context is significant as we provide evidence that BMI1 could be a reliable predictive secretory biomarker for both the races especially African-American CaP. This is evident from our data we show that E006 cell (derived from African American CaP patient) does not express PSA [14], however secrete BMI1 in culture media (Fig. 2D). Notably, E006 cell line also expressed intracellular BMI1 (Fig. 2B). This data suggest that BMI1 could be used as a biomarker for even those cases in African-American men who exhibit very low PSA levels but develop CaP disease. This corroborates to our data in Caucasian men, where we were able to detect BMI1 in patients which exhibited very low PSA levels (Table 2). Furthermore, BMI was found to independent of androgen and thus, it may be very useful as a prognostic biomarker in patients with both early as well as advanced prostate cancer. Thus, analysis of BMI1 in tissue biopsies and serum analysis may serve as a prognostic biomarker in CaP and may ultimately lead to monitoring therapeutic response during CaP treatment protocols. We suggest that BMI1 stands out as a promising molecule to be developed as an ideal serum-biomarker forBMI1:Potential Serum-Biomarker for Prostate Cancerprognosis of CaP in humans. We suggest that this study has high translational potential however, warrants further investigation in a big cohort of human patients. It is imperative that BMI1 as a biomarker be studied rigorously in parallel with drug development (which is underway in our laboratory), given the potential to maximize benefit and management of CaP disease in Caucasian as well as African-American patients, that in turn will minimize the harms and costs to society.Author ContributionsConceived and designed the experiments: MS. Performed the experiments: HRS AP WZ EJB. Analyzed the data: HRS RJK BRK EJB MS. Contributed reagents/materials/analysis tools: MS SK JSR. Wrote the paper: HRS.
Nucleic acids are highly polymorphic: depending on the sequences and environmental conditions they may exist in a variety of secondary structures such as duplexes, triplexes, tetraplexes, bulges, hairpins, loops [1,2]. Such non-canonical structures in nucleic acids are of general biological significance: they have been postulated to mediate protein-nucleic acid interactions, either by contacting protein residues directly or by producing a distinct tertiary structure 1527786 to which the protein binds [3], and to function as intermediates in the generation of frameshift mutations when errors in DNA replication occur [4,5]. In particular, extra-helical bases are thought to be implicated in nucleic acid non-canonical functions [6]. An essentially unlimited combination of secondary structural elements has been extensively described in RNA, where the single-stranded (ss) nucleic acid folds back on itself; however, DNA can also produce complex secondary structures during replication and recombination [7]. A shift of the reading frame during template-dependent DNA synthesis can lead to the addition or deletion of one or more nucleotide residues (nt.