Reviewer's report
Title:Lack of efficacy of blueberry in nutritional prevention of
azoxymethane-initiated cancers of rat small intestine and colon
Version: 1Date:19 May 2009
Reviewer: Bernadene A Magnuson
Reviewer's report:
Overall, this is a well done study. Additional information in the manuscript is
recommended as follows:
Major Compulsory Revisions
1. Background/Purpose of study: provide more details about relevance of
C-peptide; although it is indicated that its relevance to fruit consumption and
colorectal cancer development is not clear, the purpose of the study does not
clearly indicate why C-peptide was measured.
2. Background: last statement, “Results do not provide strong…” – clarify, results
of what?
3. Methods: clearly explain rationale for using rats exposed to BB throughout
gestation and lactation vs. using weanling rats.
4. Methods: clearly state what became of the dams
5. Methods: clearly state that offspring were administered AOM
6. Methods: clearly indicate the number of animals/sex/group. It was indicated
that there were 22 dams/group and litters were culled to 5 rats/sex. By my
calculation, 22 dams x 1 litter/dam x 10 offspring/litter = 220 offspring/group (110
males and 110 females). 15 rats/sex/group were killed at 6 weeks, which would
leave 95 rats/sex/group on the diets until the end of the study; however, Table 4
indicates that there were 73 to 74 rats/sex/group that were evaluated. What
happened to the missing rats?
7. Results: tumor incidences in stomach and cecum were reported to be
measured in the Methods section, but were not reported in Results section.
8. Results: p. 9, last paragraph; statement indicating that colon tumor incidence
was lower in females vs. males – add statement that this occurred regardless of
diet
9. Results: p. 10, first line; clarify that tumor incidence in female rat colon and
small intestine was unaffected by BB
10. Discussion: p. 10, first paragraph; how would decreased dietary
concentration of BB have a more protective effect in the previous study?
11. Discussion: There is a lot of speculation about the reason for the gender
differences in tumor incidence regardless of diet. Clarify as to whether there are
any historical data for the following:
a. Differences in AOM-induced colon tumors in F344 vs. Sprague-Dawley rats
b. Sex differences in AOM-induced colon tumors in Sprague-Dawley rats
c. Sex differences in number of AOM-induced ACF vs. colon tumors in this strain
d. Sex differences in progression of adenomas to adenocarcinomas in this strain
12. Discussion addressed ACF formation and overall tumor incidence, but did not
clearly discuss differences in tumor pathology, i.e., sex differences in incidence
of adenocarcinomas and effect of BB on reduction of adenocarcinomas in
females
Minor Essential Revisions
13. Define BB, AOM and PBS at first instance within body of report (Background
section)
14. Tables 3 and 4, heading: indicate time points at which measurements were
taken, i.e., at 6 and 17 weeks post-second AOM treatment, respectively (similar
to that in heading of Table 2)
15. Figure 3 Legend: indicate # animals/sex/group
Discretionary Revisions
In table 4, also add number of animals with tumors for each to clarify that the
incidence is # animals with at least one tumor, not number of tumors. Also, I find
the data in Figure 3 to be misleading. Would rather see actual number of animals
in each group with single and multiple tumors. What is the rationale for
expressing as %?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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:Lack of efficacy of blueberry in nutritional prevention of
azoxymethane-initiated cancers of rat small intestine and colon
Version: 1Date:19 May 2009
Reviewer: Bernadene A Magnuson
Reviewer's report:
Overall, this is a well done study. Additional information in the manuscript is
recommended as follows:
Major Compulsory Revisions
1. Background/Purpose of study: provide more details about relevance of
C-peptide; although it is indicated that its relevance to fruit consumption and
colorectal cancer development is not clear, the purpose of the study does not
clearly indicate why C-peptide was measured.
2. Background: last statement, “Results do not provide strong…” – clarify, results
of what?
3. Methods: clearly explain rationale for using rats exposed to BB throughout
gestation and lactation vs. using weanling rats.
4. Methods: clearly state what became of the dams
5. Methods: clearly state that offspring were administered AOM
6. Methods: clearly indicate the number of animals/sex/group. It was indicated
that there were 22 dams/group and litters were culled to 5 rats/sex. By my
calculation, 22 dams x 1 litter/dam x 10 offspring/litter = 220 offspring/group (110
males and 110 females). 15 rats/sex/group were killed at 6 weeks, which would
leave 95 rats/sex/group on the diets until the end of the study; however, Table 4
indicates that there were 73 to 74 rats/sex/group that were evaluated. What
happened to the missing rats?
7. Results: tumor incidences in stomach and cecum were reported to be
measured in the Methods section, but were not reported in Results section.
8. Results: p. 9, last paragraph; statement indicating that colon tumor incidence
was lower in females vs. males – add statement that this occurred regardless of
diet
9. Results: p. 10, first line; clarify that tumor incidence in female rat colon and
small intestine was unaffected by BB
10. Discussion: p. 10, first paragraph; how would decreased dietary
concentration of BB have a more protective effect in the previous study?
11. Discussion: There is a lot of speculation about the reason for the gender
differences in tumor incidence regardless of diet. Clarify as to whether there are
any historical data for the following:
a. Differences in AOM-induced colon tumors in F344 vs. Sprague-Dawley rats
b. Sex differences in AOM-induced colon tumors in Sprague-Dawley rats
c. Sex differences in number of AOM-induced ACF vs. colon tumors in this strain
d. Sex differences in progression of adenomas to adenocarcinomas in this strain
12. Discussion addressed ACF formation and overall tumor incidence, but did not
clearly discuss differences in tumor pathology, i.e., sex differences in incidence
of adenocarcinomas and effect of BB on reduction of adenocarcinomas in
females
Minor Essential Revisions
13. Define BB, AOM and PBS at first instance within body of report (Background
section)
14. Tables 3 and 4, heading: indicate time points at which measurements were
taken, i.e., at 6 and 17 weeks post-second AOM treatment, respectively (similar
to that in heading of Table 2)
15. Figure 3 Legend: indicate # animals/sex/group
Discretionary Revisions
In table 4, also add number of animals with tumors for each to clarify that the
incidence is # animals with at least one tumor, not number of tumors. Also, I find
the data in Figure 3 to be misleading. Would rather see actual number of animals
in each group with single and multiple tumors. What is the rationale for
expressing as %?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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:Lack of efficacy of blueberry in nutritional prevention of
azoxymethane-initiated cancers of rat small intestine and colon
Version: 1Date:19 May 2009
Reviewer: Bernadene A Magnuson
Reviewer's report:
Overall, this is a well done study. Additional information in the manuscript is
recommended as follows:
Major Compulsory Revisions
1. Background/Purpose of study: provide more details about relevance of
C-peptide; although it is indicated that its relevance to fruit consumption and
colorectal cancer development is not clear, the purpose of the study does not
clearly indicate why C-peptide was measured.
2. Background: last statement, “Results do not provide strong…” – clarify, results
of what?
3. Methods: clearly explain rationale for using rats exposed to BB throughout
gestation and lactation vs. using weanling rats.
4. Methods: clearly state what became of the dams
5. Methods: clearly state that offspring were administered AOM
6. Methods: clearly indicate the number of animals/sex/group. It was indicated
that there were 22 dams/group and litters were culled to 5 rats/sex. By my
calculation, 22 dams x 1 litter/dam x 10 offspring/litter = 220 offspring/group (110
males and 110 females). 15 rats/sex/group were killed at 6 weeks, which would
leave 95 rats/sex/group on the diets until the end of the study; however, Table 4
indicates that there were 73 to 74 rats/sex/group that were evaluated. What
happened to the missing rats?
7. Results: tumor incidences in stomach and cecum were reported to be
measured in the Methods section, but were not reported in Results section.
8. Results: p. 9, last paragraph; statement indicating that colon tumor incidence
was lower in females vs. males – add statement that this occurred regardless of
diet
9. Results: p. 10, first line; clarify that tumor incidence in female rat colon and
small intestine was unaffected by BB
10. Discussion: p. 10, first paragraph; how would decreased dietary
concentration of BB have a more protective effect in the previous study?
11. Discussion: There is a lot of speculation about the reason for the gender
differences in tumor incidence regardless of diet. Clarify as to whether there are
any historical data for the following:
a. Differences in AOM-induced colon tumors in F344 vs. Sprague-Dawley rats
b. Sex differences in AOM-induced colon tumors in Sprague-Dawley rats
c. Sex differences in number of AOM-induced ACF vs. colon tumors in this strain
d. Sex differences in progression of adenomas to adenocarcinomas in this strain
12. Discussion addressed ACF formation and overall tumor incidence, but did not
clearly discuss differences in tumor pathology, i.e., sex differences in incidence
of adenocarcinomas and effect of BB on reduction of adenocarcinomas in
females
Minor Essential Revisions
13. Define BB, AOM and PBS at first instance within body of report (Background
section)
14. Tables 3 and 4, heading: indicate time points at which measurements were
taken, i.e., at 6 and 17 weeks post-second AOM treatment, respectively (similar
to that in heading of Table 2)
15. Figure 3 Legend: indicate # animals/sex/group
Discretionary Revisions
In table 4, also add number of animals with tumors for each to clarify that the
incidence is # animals with at least one tumor, not number of tumors. Also, I find
the data in Figure 3 to be misleading. Would rather see actual number of animals
in each group with single and multiple tumors. What is the rationale for
expressing as %?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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