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Review
Peer-Review Record

Adjuvant Properties of Caffeic Acid in Cancer Treatment

Int. J. Mol. Sci. 2024, 25(14), 7631; https://doi.org/10.3390/ijms25147631
by Nicole Cortez 1, Cecilia Villegas 1, Viviana Burgos 2, Jaime R. Cabrera-Pardo 3, Leandro Ortiz 4, Iván González-Chavarría 5, Vaderament-A. Nchiozem-Ngnitedem 6 and Cristian Paz 1,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2024, 25(14), 7631; https://doi.org/10.3390/ijms25147631
Submission received: 27 May 2024 / Revised: 4 July 2024 / Accepted: 8 July 2024 / Published: 11 July 2024

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

1. Before presenting CA influence on cancer cells, I suggest describing the mechanism of how a cancer cell is formed, with particular reference to various pathways, e.g. oxidative and inflammatory, ErbB family pathway, the p53-mediated apoptosis pathway, etc. This should be presented as a separate chapter. Then the publication will be more readable and the reader will have a latitude to relate certain facts

2. Section 8 should be divided into two demonstrating both the in vitro and in vivo (animals) and in vivo (clinical) studies. The Authors provide with a separate chapter 10 with clinical data, however, in my opinion, this should be inserted as a subsection of the chapter 8. otherwise, it is quite chaotic

3. Also, the paper would be improved greatly if the authors could provide information on whether CA is effective on every cancer cell types. What types of cancer are resistant?

4. Please provide the limitation of the study

2. 

Comments on the Quality of English Language

minor changes are required

Author Response

Dear Reviewer.

We would like to thank your comments and suggestions done to our ms, we received some very similar comments from other reviewers, then we tried to do our best to give a better response to all of you. You can see that a new paragraph was added, tables, and an extensive number of citations. I hope that this new version is to your agree. 

We give response point to point of your comments.

All the best!

Dr. Cristian Paz

Reviwer 1.

(x) Minor editing of English language required

  1. Before presenting CA influence on cancer cells, I suggest describing the mechanism of how a cancer cell is formed, with particular reference to various pathways, e.g. oxidative and inflammatory, ErbB family pathway, the p53-mediated apoptosis pathway, etc. This should be presented as a separate chapter. Then the publication will be more readable and the reader will have a latitude to relate certain facts

Response: Chapter 6 about Signaling pathways affected in cancer progression was added before presenting CA influence on cancer cells.

  1. Section 8 should be divided into two demonstrating both the in vitro and in vivo (animals) and in vivo (clinical) studies. The Authors provide with a separate chapter 10 with clinical data, however, in my opinion, this should be inserted as a subsection of the chapter 8. Otherwise, it is quite chaotic

Response: Your suggestion was accepted, and the chapter was divided into 2 sections, one dealing with in vitro and in vivo assays, and another section dealing with clinical assays. In addition, we added an extra column with the specific model to Tables 3 and 4 for the reader's clarity.

  1. Also, the paper would be improved greatly if the authors could provide information on whether CA is effective on every cancer cell types. What types of cancer are resistant?

Response: Resistant Cell lines have been mentioned. It is effective in some cancers, but has not yet been tested in all cancers, so this is an issue we discuss in the conclusions as a limitation of the study.

  1. Please provide the limitation of the study

Response: Limitations of the study were added in the Conclusions section.

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

In this review authors screened the current literaure from Google Scholar, PubMed, the Phenol-Explorer database, and ClinicalTrials.gov to underscore the potential of CA in cancer prevention and overcoming chemoresistance.

The manuscript is interesting and generally well written and illustrated. However, several points deserve to be improved. My comments are listed below. 

Figure 1: Where these structures come from? did the authors took them from a free database? the source must be specified 

Line 60: Since this is a review article, authors must give a general overview of the topic treated. In particular, since oxidative stress plays a key role in this manuscript, a brief introduction on NRF2/KEAP1/ARE signaling deserves to be added. In fact, this pathway plays a key role in the onset and progression of several cancer types (see  PMID: 37525922 and PMID: 37841775 ).

2. Methodology: A flow chart reporting inclusion and exclusion criteria, as well as the number of studies obtained by each database screened deserves to be added 

Figure 2: Why L-Tyrosine and 4-Hydroxyphenylpiruvate have been reported in blue?

Table 3 and 4: it should be added a column reporting the model used in the study discussed 

A schematic figure resuming the main topics discussed in this review should be added

A graphical abstract would be helpful for the readers interested in this topic 

An accurate revision of typing errors is recommended.

An accurate revision of formatting is recommended. In particular, the presence of short paragraph and spaces among paragraphs should be avoided.

Abbreviations must be written in full length when mentioned ofr the first time

Author Response

Dear Reviewer.

We would like to thank your comments and suggestions done to our ms, we received some very similar comments from other reviewers, then we tried to do our best to give a better response to all of you. You can see that a new paragraph was added, tables, and an extensive number of citations. I hope that this new version is to your agree. 

We give response point to point of your comments.

All the best!

Dr. Cristian Paz

 

Reviewer 2

In this review authors screened the current literaure from Google Scholar, PubMed, the Phenol-Explorer database, and ClinicalTrials.gov to underscore the potential of CA in cancer prevention and overcoming chemoresistance.

The manuscript is interesting and generally well-written and illustrated. However, several points deserve to be improved. My comments are listed below. 

Figure 1: Where these structures come from? did the authors took them from a free database? the source must be specified 

Response: The source was specified. It made it by the authors using ChemDraw software.

Line 60: Since this is a review article, authors must give a general overview of the topic treated. In particular, since oxidative stress plays a key role in this manuscript, a brief introduction on NRF2/KEAP1/ARE signaling deserves to be added. In fact, this pathway plays a key role in the onset and progression of several cancer types (see  PMID: 37525922 and PMID: 37841775 ).

Response: Information on the role of oxidative stress and the NRF2/KEAP1/ARE pathway has been added in a new chapter 6 on Signaling pathways affected in cancer progression.

  1. Methodology: A flow chart reporting inclusion and exclusion criteria, as well as the number of studies obtained by each database screened deserves to be added 

Response: A flow chart was added in Methodology section.

Figure 2: Why L-Tyrosine and 4-Hydroxyphenylpiruvate have been reported in blue?

Response: It was corrected. L-Tyrosine and L-Phenilalanine were reported in blue to highlight the amino acids involved in caffeic acid biosynthesis.

Table 3 and 4: it should be added a column reporting the model used in the study discussed 

Response: We added an extra column with the specific model to Tables 3 and 4 for the reader's clarity.

A schematic figure resuming the main topics discussed in this review should be added

Response: Flowchart summarizing the activity of CA in cancer cells was added as Figure 6, Chapter 8.

A graphical abstract would be helpful for readers interested in this topic 

Response: A graphical abstract was added

An accurate revision of typing errors is recommended.

Response: It was reviewed and corrected

An accurate revision of formatting is recommended. In particular, the presence of short paragraphs and spaces among paragraphs should be avoided.

Response: It was reviewed and corrected

Abbreviations must be written in full length when mentioned for the first time

Response: It was revised and corrected.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

the manuscript can be accepted in the present form

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