Submited on: 08 Jul 2013 04:34:33 PM GMT
Published on: 09 Jul 2013 05:31:30 AM GMT
 
Cardiac Glycoside inhibition of glycolysis
Posted by Mr. Caleb Akers on 01 Nov 2017 02:47:09 PM GMT Reviewed by Interested Peers

  • What are the main claims of the paper and how important are they?

    This paper claims that the three cardiac glycosides chosen have potent inhibition of glycolysis in A549 lung cancer cells. This is especially important in the case of digitoxin, which was potent at concentrations below those in the plasma of treated patients. This research is potentially very important in the field of new cancer treatments as these drugs appear selective to cancer cells at the concentrations chosen.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    These results appear novel in respect to the methods and range of drugs used. This paper specifically uses these drugs to investigate the effect on glycolysis in both glucose redution and lactate production.


  • Are the claims properly placed in the context of the previous literature?

    The authors give sufficient literature to place their study in context.


  • Do the results support the claims? If not, what other evidence is required?

    The results shown adequately support the claims made.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    The protocol provided appears to be strictly followed.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Methods are sufficiently explained and valid for the results desired and outcomes claimed. These experiments could be repeated with the details given.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    The methods used are sufficient to prove the authors claims.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    The paper does well in explaining both how the results were gathered and interpreted while also admitting an unknown in their interpretation with repect to the connection between glycolysis inhibition and selective anticancer activity. The breadth of drugs used in this study and the conclusions drawn are sufficient to be important in the field.


  • Other Comments:

    Well written paper with only a couple minor grammatical or spelling mistakes that did not affect understanding. 

  • Competing interests:
    .
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:

    .

  • Experience and credentials in the specific area of science:

    Graduate student in pharmaceutical sciences with experience in cancer research.

  • How to cite:  Akers C .Cardiac Glycoside inhibition of glycolysis[Review of the article 'The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells ' by Lopez-Lazaro M].WebmedCentral 2013;8(11):WMCRW003375
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  • What are the main claims of the paper and how important are they?

    This paper tests the efficacy of cardiac glycosides in lung cancer inhibition in culture. Cardiac glycosides have recently been observed to have lung cancer growth inhibition effects in mice and some isolated human cases. This paper is taking the question to a higher level by testing efficacy directly in culture.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    The claims are not novel in the sense that circumstantial evidence exists in the literature suggesting use of the drug against lung cancer. This work is a more systematic approach that more directly addresses the problem.


  • Are the claims properly placed in the context of the previous literature?

    As far as I could tell, the introduction did a good job of succinctly placing the study in context of previous work while also identifying the specific cardiac glycosides used in the study: digitoxin, digoxin and ouabain.


  • Do the results support the claims? If not, what other evidence is required?

    The results show clear inhibition of lung cancer cell growth using three cardiac glycosides isolated from plants: digitoxin, digoxin and ouabain. The authors use a proper control cell line in the experiments while also clearly demonstrating that the normal mechanism of cardiac glycoside function (decrease in glucose consumption and increase in lactate) is also being observed. To test synergy, the authors also try combinations of the cardiac glycosides with cisplatin, a common lung cancer treatment. Here, the paper becomes a little confusing as the data are presented as tables, not graphes, making comprehension difficult. Nonetheless, the authors do seem to see some synergy but not with all the combinations. They also note the order in which the combinations are administered seems to be an important factor in determining the outcome. It was unfortunate that the authors did not venture in trying to explain these subtlties as they are the most novel parts of the paper.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    I saw no obvious problems with the methods. The authors seemed to use proper controls at all times. Although there were multiple repeats of the experiments, there was never any mention of the number of repeats. This information should be provided for each experiment.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Like most of the paper, the methods were very succinct but adequate.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    It was unclear to me why the different combinations of cardiac glycoside and cisplatin were behaving differently. It would have been nice to have more mention of this in the discussion so the authors could at least speculate about the mechanism. As it stands, the observation seems interesting but very unresolved. The issue of the order in which reagents were administered also seems to be an interesting observation the authors could have dwelled on more. As it stands, the majority of the paper only confirms what the reader expects from previous work without necessarily opening a compelling avenue of new discussion.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    The first half of the paper is quite good. The main experiments examining cardiac glycoside efficacy and glucose, lactate were very well done and clear. The work on combinations, however, leaves the reader feeling unresolved. At the very least it would have been nice for the authors to offer some speculations or possible directions for future work.

    As it stands now, this paper is quite good: a couple more better figures and a longer discussion away from being of similar quality to peer-reviewed work in other journals. I note again that the paper, as it stands now, only emphasizes what the reader already expects from previous work. The authors should put more effort into opening a new avenue of discussion.


  • Other Comments:

    One of the things I was curious about was whether the observed growth inhibition was due to cell death or true inhibition. This distinction was sometimes muddled in the language of the paper. One can assume that the cells are starving on some level given the glucose and lactate data but no statement was made about this distinction. Fig 1 suggests direct cell death but no explanation was given as to how the y-axis was normalized so the reader can not be sure. Perhaps more careful language to outline this distinction would be useful.

  • Competing interests:
    None
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    Cancer biology.

  • How to cite:  Fendos J .Close to a complete work of level similar to traditional peer-reviewed journals.[Review of the article 'The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells ' by Lopez-Lazaro M].WebmedCentral 2013;4(7):WMCRW002798
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Cardiac glycosides and lung cancer cells
Posted by Prof. Valcinir Bedin on 12 Jul 2013 12:11:57 AM GMT

  • What are the main claims of the paper and how important are they?

    The claims are the relation between the cardiac glycosides digitoxin, digoxin and ouabain and the their inhibition role in lung cells, and they are very important to point out this new pathway to cancer treatment.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Yes they are novel claims


  • Are the claims properly placed in the context of the previous literature?

    Yes


  • Do the results support the claims? If not, what other evidence is required?

    Yes


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    The protocol provided is ok andthere is no deviations from it.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Yes. With the methodology provided one could reproduce it.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    We hope to read a paper soon with improvement of of this work, for instance, with animal subjects


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    Yes because it puts a light on the lung cancer therapy.


  • Other Comments:

    No

  • Competing interests:
    None
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    Yes
  • References:

    Fractal dimension as a predective item in melanoma

  • Experience and credentials in the specific area of science:

    I have been teachn medicine for the last 30 years and I have a master and doctorship in skin cancer

  • How to cite:  Bedin V .Cardiac glycosides and lung cancer cells[Review of the article 'The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells ' by Lopez-Lazaro M].WebmedCentral 2013;4(7):WMCRW002791
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  • What are the main claims of the paper and how important are they?

    To study role of certain cardiac glycosides in management of lung cancer


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Yes


  • Are the claims properly placed in the context of the previous literature?

    Yes


  • Do the results support the claims? If not, what other evidence is required?

    Yes


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    Yes


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Yes


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    I have some suggestions as below-

    1. This study has been carried out in laboratory. i would be happy to see its actual results on animal models & subsequently on human beings & its real outcome when we can promote this novel concept in treatment of lung cancer.
    2. What will be the cost of this treatment & how long it will be needed for complete cure also needs to be mentioned for future studies.
    3. Overall it is a nice attempt as new dimension in treatment of lung cancer.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    Yes as it is adding a new dimension towards the treatment of lung cancer.


  • Other Comments:

    No

  • Competing interests:
    None
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:

    No

  • Experience and credentials in the specific area of science:

    I am working as in charge of cancer program of my institute where such experimental work is carried out for better management of cancer.

  • How to cite:  Belekar D M.The cardiac glycosides digitoxin, digoxin & ouabain induce a potent inhibition of glycolysis in lung cancer cells[Review of the article 'The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells ' by Lopez-Lazaro M].WebmedCentral 2013;4(7):WMCRW002788
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