Targeting Hyaluronan Synthesis in Cancer: A Road Less Travelled

Round 1

Reviewer 1 Report

This is an interesting review that focuses hyaluronan synthesis in cancer.

Nevertheless, pioneering, and significant works on the subject were not cited. Some of these works are:

(1) Passerotti CC, Bonfim A, Martins JR, Dall'Oglio MF, Sampaio LO, Mendes A, Ortiz V, Srougi M, Dietrich CP, Nader HB. Urinary hyaluronan as a marker for the presence of residual transitional cell carcinoma of the urinary bladder. Eur Urol. 2006 Jan;49(1):71-5;

(2) Passerotti CC, Srougi M, Bomfim AC, Martins JR, Leite KR, Dos Reis ST, Sampaio LO, Ortiz V, Dietrich CP, Nader HB. Testing for urinary hyaluronate improves detection and grading of transitional cell carcinoma. Urol Oncol. 2011 Nov-Dec;29(6):710-5;

(3) Jeronimo SM, Sales AO, Fernandes MZ, Melo FP, Sampaio LO, Dietrich CP, Nader HB. Glycosaminoglycan structure and content differ according to the origins of human tumors. Braz J Med Biol Res. 1994 Sep;27(9):2253-8.

The first two papers describe a very sensitive methodology to quantify hyaluronan and have shown that urinary hyaluronan may be used as a tumor marker to aid in diagnosing and grading transitional cell carcinoma, which is responsible for 90% of bladder tumors.

The third paper describes the glycosaminoglycan composition of a nephroblastoma of embryonic origin, the Wilms' tumor. The authors have shown that hyaluronan concentration is increased in Wilms’ tumor.

Citing these works can enrich and strengthen the article's statements, especially in item 4, page 3. 

Author Response

I thank the reviewer for his valuable comments that led to an improved version of the manuscript. I have addressed the reviewer comment by including the significant works proposed in a separate paragraph that I added in section 4, describing the role of hyaluronan as a biomarker in tumours. The respective section is marked with red colour in the revised text.

Reviewer 2 Report

I find the article entitled “Targeting hyaluronan synthesis in cancer: a road less traveled” very interesting. However, to improve the quality of the paper, I have the following suggestions:

1.     In section 2.1, the author is advised to include the importance of very high molecular weight hyaluronan in cancer resistance.

2.     It would be good if the author could provide a figure explaining the effect of different drugs on hyaluronan synthesis.

3.     The author is advised to describe the mode of action of DDIT in detail in Section 5.1.

4.     I also suggest the author review more relevant papers to make the review paper more interesting.

Minor editing of English language required

Author Response

I thank the reviewer for his valuable comments that led to an improved version of the manuscript. I have addressed the comments made by the reviewer as outlined below:

1. I included the role of very high molecular weight hyaluronan in cancer resistance in the text but in section 4 instead of section 2.1.
2. I have provided a figure and a table explaining the drug effects on different types of tumours.
3. Unfortunately, in that study we were not able to pinpoint the exact mechanism of DDIT. I have amended the requested text by including all available information from the initial study.
4. Throughout the text I added several more relevant paper.

The reviewer can find all the corrections marked in red throughout the text.