Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells
, Jun Woo Kim 1,2,†, Dae Kyung Kim 3,†, Dong Kyu Choi 1, Seul Lee 1, Ji Hoon Yu 1,2, Oh-Bin Kwon 1, Jungsul Lee 4, Dong-Seok Lee 2,*, Jae Ho Kim 3,* and Sang-Hyun Min 1,*Round 1
Reviewer 1 Report
The manuscript is of great importance. The presented results might be potentially relevant for the clinical implementation. However, the revision proposed below may further improve the overall quality of the publication.
- It is strongly recommended to elaborate on the "Abstract" providing more clear statements and precise formulation regarding the specificity of the proposed treatment targets for CSC. Formulations regarding the focus of the study and achievements such as "a few CSCs may remain...", "Interestingly, CCBs..." "Surprisingly, expression of... genes..." should be essentially reconsidered making the message more clear to the readers and to present the hypothesis and results in terms of their scientific and clinical utility.
- "Discussion" should be presented in more reader-friendly way by presenting individual paragraphs supplied with corresponding sub-titles which would serves as the paper-relevant messages such as - "Ovarian cancer is associated with high recurrence rate"; - "CCBs induce apoptosis in glioblastoma cells"; -"Knockdown VGCC genes reduces stemness in CSCs" etc.
- The study limitation should be discussed.
- Finally, it is strongly recommended to provide paragraphs for outlook to demonstrate how the presented achievements may potentially improve medical services and what is needed for that. Doing that the authors are kindly requested to refer to the recently published (2018-2020) field-relevant papers. Some of them are exemplified below.
- Advanced predictive and personalised medical approach in management of ovarian cancer:
Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer. doi: 10.1007/s13167-019-00175-0.
Signaling pathway network alterations in human ovarian cancers identified with quantitative mitochondrial proteomics. doi: 10.1007/s13167-019-00170-5.
- Crucial role of multiomic approach in cancer prediction and treatment
Preventive, predictive, and personalized medicine for effective and affordable cancer care. doi: 10.1007/s13167-018-0130-1.
The crucial role of multiomic approach in cancer research and clinically relevant outcomes. doi: 10.1007/s13167-018-0128-8.
Author Response
March. 24. 2020
Dear reviewer
Thank you for having our manuscript “Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells.” (IJMS-751079) reviewed and giving valuable comments. We tried to faithfully and reasonably address questions raised and accommodate recommendations made during reviewing process. I am here with enclosing revised manuscript and our responses to the reviewer’s comments.
We hope this re-submission fulfills the concerns and requirements in a reasonable manner and will be reconsidered our manuscript suitable for publication in the IJMS.
We thank you for the help, and look forward to favorable results.
Sincerely,
Sang-Hyun Min, Ph. D.
Deputy Director/Chief
New Drug Development Center, DGMIF,
Daegu 41061, Republic of Korea.
Fax: 82-53-790-5799
E-mail: [email protected]
Reviewer 2 Report
The authors have investigated the effect of calcium inhibitors, in ovarian cancer stem cells. The report that they have found four calcium channel blockers, which manifested anticancer effects against ovarian CSC by reducing stemness and inducing apoptosis. Their results indicated that the CSC model provides an innovative high-throughput platform for a simple, easy, and cost-effective method to screen anti-CSC drugs, and that calcium channels can be novel therapeutic targets for ovarian CSCs.
Their work is interesting and it has merit for publication, after addressing the following comments.
First of all, the aim of the paper is not clear. Is it to present a new high-throughput method for screening of cytotoxic compounds or to investigate the effects of calcium blockers? this should be stated in the "Introduction" section, where the "aim" should be clearly stated.
The authors, should also give some more reasoning on their choice to test calcium blockers. In their manuscript they refer to their selection as a choice made by the discovery that 4 out of 15 chemicals were calcium channel blockers. please elaborate more on this selection. was it random? what were the other 11 chemicals?
For cell cycle analysis, did they perform RNAase treatment, as it is possible tha RNA interferred with PI. In addition, what was the software of choice for cell cycle analysis? Further on, how did they decide where the limits of apoptosis were in Figure 3A?
Finally, they should highlight their findings at the end of the "discussion" section and refer to the use of the investigated chemicals as potential treatments for ovarian cancer, as well as provide some future directions and the limitations of their study.
The authors have performed a great deal of experiments to support their work. Yet, they should pose their initial hypothesis and in addition they should be more concise on the aims of their work.
Author Response
March. 24. 2020
Dear Reviewer
Thank you for having our manuscript “Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells.” (IJMS-751079) reviewed and giving valuable comments. We tried to faithfully and reasonably address questions raised and accommodate recommendations made during reviewing process. I am here with enclosing revised manuscript and our responses to the reviewer’s comments.
We hope this re-submission fulfills the concerns and requirements in a reasonable manner and will be reconsidered our manuscript suitable for publication in the IJMS.
We thank you for the help, and look forward to favorable results.
Sincerely,
Sang-Hyun Min, Ph. D.
Deputy Director/Chief
New Drug Development Center, DGMIF,
Daegu 41061, Republic of Korea.
Fax: 82-53-790-5799
E-mail: [email protected]
