Reviewer's report
Title:Up-Regulation of CNDP2 Facilitates the Proliferation of Colon Cancer
Version: 1Date:2 October 2013
Reviewer: Wim Derave
Reviewer's report:
The current study explores the hypothesis that CNDP2 could be the link between
potential beneficial therapeutic effects of carnosine and bestatin in oncology. The
study is certainly valuable as it contains results from both patients and cells and
animal model, which all more or less point into the same direction that CNDP2 is
a potential therapeutic target for colon cancer.
The major concern relates to the fact that there is large controversy as to
whether carnosine is in fact a substrate of CN2, the enzyme produced by the
CNDP2 gene. Teufel et al. (JBC 2003) suggest that carnosine is not a substrate
under physiological conditions (so CNDP2 must have another function), whereas
Pandya et al. (Anal Biochem 2011) suggest it can cleave carnosine. This aspect
should be elaborated in both the introduction and the discussion and more
caution should be included.
Please also provide a description of the metabolism and (patho)physiological role
of carnosine and the role of the carnosinases herein (see recent review by
Boldyrev, Aldini & Derave, Physiological Reviews 2013).
Related to the above comment, in the discussion, the authors refer to the
signaling cascade in which CNDP2 is involved. This is not clear to me what is
meant here. I do not think CNDP2 is involved in a signaling cascade, but
products of enzymatic reaction may affect these proteins. The link between
EGFR, cyclin B1, cyclin E and carnosinase is unclear. These should not be
mentioned as ‘playing an important role’ as mentioned in the conclusions.
Page 4, line 13-14: The sentence ‘The CM samples consisted….’ is followed by
the sentence: ‘These samples displayed strong cytoplasmic staining…’. I think
this can lead to confusion as the CM show the weakest staining.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Up-Regulation of CNDP2 Facilitates the Proliferation of Colon Cancer
Version: 1Date:2 October 2013
Reviewer: Wim Derave
Reviewer's report:
The current study explores the hypothesis that CNDP2 could be the link between
potential beneficial therapeutic effects of carnosine and bestatin in oncology. The
study is certainly valuable as it contains results from both patients and cells and
animal model, which all more or less point into the same direction that CNDP2 is
a potential therapeutic target for colon cancer.
The major concern relates to the fact that there is large controversy as to
whether carnosine is in fact a substrate of CN2, the enzyme produced by the
CNDP2 gene. Teufel et al. (JBC 2003) suggest that carnosine is not a substrate
under physiological conditions (so CNDP2 must have another function), whereas
Pandya et al. (Anal Biochem 2011) suggest it can cleave carnosine. This aspect
should be elaborated in both the introduction and the discussion and more
caution should be included.
Please also provide a description of the metabolism and (patho)physiological role
of carnosine and the role of the carnosinases herein (see recent review by
Boldyrev, Aldini & Derave, Physiological Reviews 2013).
Related to the above comment, in the discussion, the authors refer to the
signaling cascade in which CNDP2 is involved. This is not clear to me what is
meant here. I do not think CNDP2 is involved in a signaling cascade, but
products of enzymatic reaction may affect these proteins. The link between
EGFR, cyclin B1, cyclin E and carnosinase is unclear. These should not be
mentioned as ‘playing an important role’ as mentioned in the conclusions.
Page 4, line 13-14: The sentence ‘The CM samples consisted….’ is followed by
the sentence: ‘These samples displayed strong cytoplasmic staining…’. I think
this can lead to confusion as the CM show the weakest staining.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Up-Regulation of CNDP2 Facilitates the Proliferation of Colon Cancer
Version: 1Date:2 October 2013
Reviewer: Wim Derave
Reviewer's report:
The current study explores the hypothesis that CNDP2 could be the link between
potential beneficial therapeutic effects of carnosine and bestatin in oncology. The
study is certainly valuable as it contains results from both patients and cells and
animal model, which all more or less point into the same direction that CNDP2 is
a potential therapeutic target for colon cancer.
The major concern relates to the fact that there is large controversy as to
whether carnosine is in fact a substrate of CN2, the enzyme produced by the
CNDP2 gene. Teufel et al. (JBC 2003) suggest that carnosine is not a substrate
under physiological conditions (so CNDP2 must have another function), whereas
Pandya et al. (Anal Biochem 2011) suggest it can cleave carnosine. This aspect
should be elaborated in both the introduction and the discussion and more
caution should be included.
Please also provide a description of the metabolism and (patho)physiological role
of carnosine and the role of the carnosinases herein (see recent review by
Boldyrev, Aldini & Derave, Physiological Reviews 2013).
Related to the above comment, in the discussion, the authors refer to the
signaling cascade in which CNDP2 is involved. This is not clear to me what is
meant here. I do not think CNDP2 is involved in a signaling cascade, but
products of enzymatic reaction may affect these proteins. The link between
EGFR, cyclin B1, cyclin E and carnosinase is unclear. These should not be
mentioned as ‘playing an important role’ as mentioned in the conclusions.
Page 4, line 13-14: The sentence ‘The CM samples consisted….’ is followed by
the sentence: ‘These samples displayed strong cytoplasmic staining…’. I think
this can lead to confusion as the CM show the weakest staining.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
assistant