Reviewer's report
Title:Epithelial to Mesenchimal transition in the liver field: the double face of
Everolimus in vitro
Version:2Date:8 April 2015
Reviewer: Itxarone Bilbao
Reviewer's report:
Discretionary revisions
The real roll of Everolimus on HCC is of outstanding merit and interest in the field
of oncology and also in the field of liver transplantation. The initial introduction of
Everolimus in the field of transplantation was at higher doses than used in clinical
practice and the doses that are recommended at present time. So the manuscript
should be useful to search an adequate dosing. The methodology is appropriate
and well described. The data exposition, the figures, the discussion and
conclusions are adequately supported by the data. The manuscript is well written
and easily understandable.
Translation from laboratory cells experiments or from small laboratory animals to
humans is very complex, especially in hepatocellular carcinoma. In that sense I
would suggest to mention this limitation in the discussion:
1.- What we name “hepatocellular carcinoma” is a variety of complex tumors that
probably employ several pathways in the different carcinogenesis phases:
initiation, promotion and expansion and also in the different phases of underlying
tissue (normal liver, fibrotic liver, cirrhotic liver). Among all these variations the
authors has tested only one type of liver cancer cells in one particular phase,
which could not be reproducible with other hepatocarcinoma developed in a
different patient with a different underlying liver disease stage.
2.- Laboratory cell experimental trials in my opinion are good models to study the
genetics of cancer, but no to study the epigenetic surrounding the
carcinogenesis. Please mention this limitation in the discussion
3.- Translation from small laboratory animals to human, should be reassured with
clinical trials. Perhaps the hepatic stellate cells on normal rats have not the same
behavior as HSC on cirrhotic human’s beings.
In summary, I would recommend to add in the discussion, comments on the
paper from Bugelski PJ with an excellent review about preclinical approaches,
evaluating the impact of immunosuppressive drugs on carcinogenesis
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: I have received funding to assist different national and
international congress from Novartis, Astellas, Pfizer and Roche
Reviewer's report
Title:Epithelial to Mesenchimal transition in the liver field: the double face of
Everolimus in vitro
Version:2Date:8 April 2015
Reviewer: Itxarone Bilbao
Reviewer's report:
Discretionary revisions
The real roll of Everolimus on HCC is of outstanding merit and interest in the field
of oncology and also in the field of liver transplantation. The initial introduction of
Everolimus in the field of transplantation was at higher doses than used in clinical
practice and the doses that are recommended at present time. So the manuscript
should be useful to search an adequate dosing. The methodology is appropriate
and well described. The data exposition, the figures, the discussion and
conclusions are adequately supported by the data. The manuscript is well written
and easily understandable.
Translation from laboratory cells experiments or from small laboratory animals to
humans is very complex, especially in hepatocellular carcinoma. In that sense I
would suggest to mention this limitation in the discussion:
1.- What we name “hepatocellular carcinoma” is a variety of complex tumors that
probably employ several pathways in the different carcinogenesis phases:
initiation, promotion and expansion and also in the different phases of underlying
tissue (normal liver, fibrotic liver, cirrhotic liver). Among all these variations the
authors has tested only one type of liver cancer cells in one particular phase,
which could not be reproducible with other hepatocarcinoma developed in a
different patient with a different underlying liver disease stage.
2.- Laboratory cell experimental trials in my opinion are good models to study the
genetics of cancer, but no to study the epigenetic surrounding the
carcinogenesis. Please mention this limitation in the discussion
3.- Translation from small laboratory animals to human, should be reassured with
clinical trials. Perhaps the hepatic stellate cells on normal rats have not the same
behavior as HSC on cirrhotic human’s beings.
In summary, I would recommend to add in the discussion, comments on the
paper from Bugelski PJ with an excellent review about preclinical approaches,
evaluating the impact of immunosuppressive drugs on carcinogenesis
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: I have received funding to assist different national and
international congress from Novartis, Astellas, Pfizer and Roche
Please review this paper.
user
Reviewer's report
Title:Epithelial to Mesenchimal transition in the liver field: the double face of
Everolimus in vitro
Version:2Date:8 April 2015
Reviewer: Itxarone Bilbao
Reviewer's report:
Discretionary revisions
The real roll of Everolimus on HCC is of outstanding merit and interest in the field
of oncology and also in the field of liver transplantation. The initial introduction of
Everolimus in the field of transplantation was at higher doses than used in clinical
practice and the doses that are recommended at present time. So the manuscript
should be useful to search an adequate dosing. The methodology is appropriate
and well described. The data exposition, the figures, the discussion and
conclusions are adequately supported by the data. The manuscript is well written
and easily understandable.
Translation from laboratory cells experiments or from small laboratory animals to
humans is very complex, especially in hepatocellular carcinoma. In that sense I
would suggest to mention this limitation in the discussion:
1.- What we name “hepatocellular carcinoma” is a variety of complex tumors that
probably employ several pathways in the different carcinogenesis phases:
initiation, promotion and expansion and also in the different phases of underlying
tissue (normal liver, fibrotic liver, cirrhotic liver). Among all these variations the
authors has tested only one type of liver cancer cells in one particular phase,
which could not be reproducible with other hepatocarcinoma developed in a
different patient with a different underlying liver disease stage.
2.- Laboratory cell experimental trials in my opinion are good models to study the
genetics of cancer, but no to study the epigenetic surrounding the
carcinogenesis. Please mention this limitation in the discussion
3.- Translation from small laboratory animals to human, should be reassured with
clinical trials. Perhaps the hepatic stellate cells on normal rats have not the same
behavior as HSC on cirrhotic human’s beings.
In summary, I would recommend to add in the discussion, comments on the
paper from Bugelski PJ with an excellent review about preclinical approaches,
evaluating the impact of immunosuppressive drugs on carcinogenesis
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: I have received funding to assist different national and
international congress from Novartis, Astellas, Pfizer and Roche
assistant