Fenbendazole Exhibits Differential Anticancer Effects In Vitro and In Vivo in Models of Mouse Lymphoma
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors presented a research paper on elucidating the potential anticancer effect of Fenbendazole in vitro and in vivo. Authors presented an interesting research, overall good experimental design and provided thorough discussion of their results. However, few questions have been risen that could be addressed by the authors in their manuscript.
Line 8. First sentence, verb is missing.
How do you comment on absence of early apoptosis in Hoechst 33342/PI staining experiment, and detection of higher incidence of early apoptosis when higher (0.1 µg/ml) of FBZ concentration was used in Annexin/PI staining? What was the rationale for 72h treatment when it comes to Hoechst 33342/PI staining opposed to 48h treatment when cells were stained with Annexin V/PI?
What was the criteria for determination of time points for drug administration for in vivo study?
What is the mechanism behind stronger binding of FBZ to the β-tubulin in parasite cells than in mammal cells. Could that be one of the reasons for observed differences between in vitro and in vivo anticancer activity of FBZ?
Author Response
Please find our reply in the attached file.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe present work reports the in vitro and in vivo biological evaluation of an antiparasitic drug, Febendazole, repositioned for its anticancer potential, here directed against lymphoma cells.
The work is fairly well presented, but its rationale is not sufficiently highlighted: in what context is it positioned? Why a specific evaluation on a lymphoma cell line? In addition, the in vitro results consistently found FBZ to be more effective than CHOP, even though CHOP is a combination of cytotoxic agents effective against lymphoma cells: how can this be explained? Are the concentrations of FBZ and CHOP used correctly proportioned?
Other remarks should be brought to the authors' attention.
- lines 2-3: the title of the article doesn't seem to be grammatically correct and should instead be written: "Fenbendazole exhibits differential anticancer effects in vitro and in vivo in models of mouse lymphoma"
- line 8: a verb is missing in this sentence.
- line 10: sentence unclear, please reword.
- lines 14-15: sentence unclear, please reword.
- line 16: please do not use “&”.
- line 16: what dose implies the starry-sky pattern?
- line 31: isn't it the increase in ROS that is associated with an anti-cancer effect? This is not clear.
- line 45: please write “there is a dearth”.
- line 57: please write “University”.
- line 72: please write “CO2” with 2 in subscript.
- line 146, 204, 205: please write “IC50” with 50 in subscript.
- lines 166, 168, 334: “compared to control” is a less cumbersome formulation than “compared to that of the control”
- line 226: please write “mm3” with 3 in superscript.
- line 360: please write “pembrolizumab (Keytruda®)”.
- line 363: please replace “Keytruda” by “pembrolizumab”.
- line 392: please write “FBZ showed in vitro anticancer effects”.
- line 394: please replace “evident” by “evidenced”.
- line 395: please replace “altered” by “alteration”.
Comments on the Quality of English LanguageModerate editing of English language required
Author Response
Please find our reply in the attached file.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsI acknowledge the modifications made by the authors, although I note that the points concerning context and rationale were not addressed in the manuscript, as expected.
