Carbon Nanotubes under Scrutiny: Their Toxicity and Utility in Mesothelioma Research
Round 1
Reviewer 1 Report
In this review, the authors discussed the role of carbon nanotubes (CNT) in mesotheliomagenesis. Given the increasing industrial use of CNT, it is likely that the carcinogenic effect of CNT in the etiology of mesothelioma will become an area of intensive research. The great amount of information provided in the review will assist other researchers in their work on finding the cure for mesothelioma. I have some minor comments.
Line 142-143: If mesothelioma can occur more than 30 years after exposure and the use of asbestos was mostly banned in the 1980s, why would a peak incidence of mesothelioma be expected to occur in 2030?
Line 145-146: Please provide the reference from which the information of 15 more month survival was obtained.
Author Response
Response to Reviewer 1 Comments
In this review, the authors discussed the role of carbon nanotubes (CNT) in mesotheliomagenesis. Given the increasing industrial use of CNT, it is likely that the carcinogenic effect of CNT in the etiology of mesothelioma will become an area of intensive research. The great amount of information provided in the review will assist other researchers in their work on finding the cure for mesothelioma. I have some minor comments.
Line 142-143: If mesothelioma can occur more than 30 years after exposure and the use of asbestos was mostly banned in the 1980s, why would a peak incidence of mesothelioma be expected to occur in 2030?
The referee is right. We corrected this mistake accordingly based on the reference #58.
Line 145-146: Please provide the reference from which the information of 15 more months survival was obtained.
A reference is now incorporated (#61).
Reviewer 2 Report
The manuscript is well written and organized. I have no particular issues to highlight and I think that the suggested topic is relevant for the scientific community.
Author Response
Response to Reviewer 2 Comments
The manuscript is well written and organized. I have no particular issues to highlight and I think that the suggested topic is relevant for the scientific community.
We thank this reviewer for this positive comment.
Reviewer 3 Report
Orsi et al present a review on the toxicity of Carbon Nanotubes (CNT) with a focus on mesothelioma. They propose that due to their engineered diversity, CNT can also be a tool for mesotheliom research.
The topic of the article is interesting an timely and the authors have contributed important original research to the field under review.
Some relevant points, however, need to be addressed by the authors before this review is suitable for publication.
Specifically:
Lines 33-41: Refs 1 and 2 are described as „Simultaneously,….“ Yet, Ref 1 is from the year 2000 and Ref 2 from 1994.
Lines 122-123: The statement that CNT can act as free radical scavengers need further expansion and explanation
Figure 1: The text in the Figure is too small and too low resolution and is therefore hard to read. Abbreviations used in the Figure (CNT-M, CNT-7 etc.) are not explained. The references used in the Figure also need to be numbered in the same style as those in the text to help identify them in the bibliography. The heading „historical progression of CNT-induced toxicity“ makes no sense, as the figure presents a research timeline. Also the timeline ends with 2016, which does not appear to be very up to date.
Line 160: The term „mesotheliomagenic cell lines“ is not clear. Are these mesothelioma cell lines from patients, transgenic mouse lines or something else?
Figure 3: The low magnification and low resolution make it impossible to recognize much in this Figure. The mentioned Hoechst counterstaining, for instance, is completely invisible.
The last part (5.2 until line 354) reads more like a presentation of preliminary data from the authors´ research than like a balanced review article. More comparison to related research should be attempted.
Generally, a thorough proofreading of the text needs to be performed as there are multiple omissions and other mistakes. E.g. line 83: „extensive vitro“, line 171:“ Asbestos fibers“, line 183: „Whether“ probably should mean „When“ etc.
In all Figures, the Figure legends need to be separated better from the main text
Author Response
Response to Reviewer 3 Comments
Orsi et al present a review on the toxicity of Carbon Nanotubes (CNT) with a focus on mesothelioma. They propose that due to their engineered diversity, CNT can also be a tool for mesotheliom research.The topic of the article is interesting an timely and the authors have contributed important original research to the field under review.Some relevant points, however, need to be addressed by the authors before this review is suitable for publication.
Specifically:
Lines 33-41: Refs 1 and 2 are described as „Simultaneously,….“ Yet, Ref 1 is from the year 2000 and Ref 2 from 1994.
We agree and removed the word “Simultaneously”.
Lines 122-123: The statement that CNT can act as free radical scavengers need further expansion and explanation.
We considered this point and detailed our findings on scavenger capacity of CNT (line 122).
Figure 1: The text in the Figure is too small and too low resolution and is therefore hard to read. Abbreviations used in the Figure (CNT-M, CNT-7 etc.) are not explained. The references used in the Figure also need to be numbered in the same style as those in the text to help identify them in the bibliography. The heading „historical progression of CNT-induced toxicity“ makes no sense, as the figure presents a research timeline. Also the timeline ends with 2016, which does not appear to be very up to date.
We agree with the reviewer and modified the figure and timeline accordingly (higher magnification and resolution). The title, legend and references were also modified as required.
Line 160: The term „mesotheliomagenic cell lines“ is not clear. Are these mesothelioma cell lines from patients, transgenic mouse lines or something else?
This reviewer is right, and we corrected the text accordingly.
Figure 3: The low magnification and low resolution make it impossible to recognize much in this Figure. The mentioned Hoechst counterstaining, for instance, is completely invisible.
We improved the quality of the Figure 3 (and the other figures) and simplified its legend.
The last part (5.2 until line 354) reads more like a presentation of preliminary data from the authors´ research than like a balanced review article. More comparison to related research should be attempted.
We agree that an experimental part inserted in a review paper is not conventional and is disturbing. However, the goal of this section is to generate the interest of the reader for the novel technologies and methods for phenotyping macrophages. This part also supports that the number of accumulated macrophages per se is not anymore, an absolute key parameter for determining toxic potential of particles. Finally, the comparison with related research and findings is already presented in point 5.1.
Generally, a thorough proofreading of the text needs to be performed as there are multiple omissions and other mistakes. E.g. line 83: „extensive vitro“, line 171:“ Asbestos fibers“, line 183: „Whether“ probably should mean „When“ etc.
We thank the reviewer for pointing out these mistakes. As required, a careful rereading of the manuscrit has been done.
In all Figures, the Figure legends need to be separated better from the main text.
This point is now integrated in the new version.
Round 2
Reviewer 3 Report
Most concerns have been appropritately addressed.
However, the authors refer to a discussion of other studies in point 5.1 but there is no point 5.1.
If the authors mean point 4.1. then this section contains only a discussion of toxicity studies but no comparison to other omics data that have been performed with CNT.
While some original data can be presented in reviews, the same standards then should apply as for original data presentation in research reports. Figure 4 presents a cartoon of the omics workflow, while results are only mentioned in the text without any information on statistics, repeats etc.
Being a review article, this section needs to include a comparison to other omics studies that have been performed with CNT-treated cells/tissues.
Author Response
Last comment of Reviewer 3:
However, the authors refer to a discussion of other studies in point 5.1 but there is no point 5.1.
If the authors mean point 4.1. then this section contains only a discussion of toxicity studies but no comparison to other omics data that have been performed with CNT.
While some original data can be presented in reviews, the same standards then should apply as for original data presentation in research reports. Figure 4 presents a cartoon of the omics workflow, while results are only mentioned in the text without any information on statistics, repeats etc.
Being a review article, this section needs to include a comparison to other omics studies that have been performed with CNT-treated cells/tissues.
We regret this misunderstanding. The incorrect section numbering and new paging generated by the journal from our initial word document confused us. We agree with this comments and removed the text referring to our preliminary data.
