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), Innovative Developments in Architecture, Engineering and Construction.
| null | null |
Nevertheless, only 47.8% of them selected agreed/strongly agree regarding the statements that their ideal spot for vacation would be a wilderness area (NR1-Q12).
| null | null |
buildings12040417_makarova
| 0 |
The sentence was rewritten to demonstrate this argument.
| null | null |
Intercorrelations between responses of three subscales.
| null | null |
buildings12040417_makarova
| 0 |
d) The correlation results support the importance of biophilic design from the user perspectives.
| null | null |
However, further research on developing building typology-based biophilic design guide-lines and assessment methods are necessary.
| null | null |
buildings12040417_makarova
| 0 |
Although this I don’t believe this would be a large undertaking, the analysis would be better served by non-parametric tests due to the level of measurement used (i.e.
| null | null |
There are overlaps between the nine biophilic design attributes and these eight influential factors for the workplace.
| null | null |
buildings12040417_makarova
| 0 |
d) The correlation results support the importance of biophilic design from the user perspectives.
| null | null |
There are overlaps between the nine biophilic design attributes and these eight influential factors for the workplace.
| null | null |
buildings12040417_makarova
| 0 |
Response 16: Thanks for the reminder, the error has been corrected in the revised version.
| null | null |
Biophilia: Does Visual Contact with Nature Impact on Health and Well-Being?
| null | null |
buildings12040417_makarova
| 0 |
Effects of biophilic indoor environment on stress and anxiety recovery: a between-subjects experiment in virtual reality.
| null | null |
This would make it easier for the reader; 2) Round the percentages to the nearest whole number.
| null | null |
buildings12040417_makarova
| 0 |
This led me to believe that this office was much larger than the building studied in China.
| null | null |
Cheung, T., Schiavon, S., Graham, L.T., Tham, K.W., 2021.
| null | null |
buildings12040417_makarova
| 0 |
Revision in Page 15-17 Line 399-433: The analysis of individual items provides more details into the works' responses.
| null | null |
In the future study, the research scope should be narrow down for intensive investigation.
| null | null |
buildings12040417_makarova
| 0 |
b) Additionally, the study provides novel design guidelines for designers with emphasizing on weight for workplace design practices.
| null | null |
In-lieu of the mean, please consider using the median and inter-quartile range as the central tendency and dispersion indicators.
| null | null |
buildings12040417_makarova
| 0 |
Revision in Page 1 Line 28:“The term "Biophilia" is evolved from human evolution research and is coined to de-scribe humans' inherent love affinity for the living things in the natural world [1,2].” Point 2: P1, L39-41: Please provide references to these frameworks.
| null | null |
While this is somewhat accurate, it might be more appropriate to elucidate this as an “inherent affinity”.
| null | null |
buildings12040417_makarova
| 0 |
Physiological and cognitive performance of exposure to biophilic indoor environment.
| null | null |
These are exploited to show a new biophilic design framework for the workplace according to the users’ points of view (based on the POE results).
| null | null |
buildings12040417_perova
| 0 |
There are overlaps between the nine biophilic design attributes and these eight influential factors for the workplace.
| null | null |
Both classifications validated by previous literatures.
| null | null |
buildings12040417_perova
| 0 |
The median (IQR) value of the POE scale BDE is evaluated as 42.00 (5.00) (range of total value: min.
| null | null |
Environmental Quality and the Productive Workplace.
| null | null |
buildings12040417_perova
| 0 |
2) However, these patterns are not common in most offices.
| null | null |
Hence, all the means (SD) are replaced as medians (IQR).
| null | null |
buildings12040417_perova
| 0 |
In my view, POE information had more utility diagnosing operation problems, which can be solved when running the building, identifying prominent sources of dissatisfaction that can prompt action to resolve these issues.
| null | null |
Revision in Page 3 Line 109: “It has helped experts to obtain user’s feedbacks over the last five decades [31,32].” Point 6: P3, L106: While I generally agree with, questions could be raised to whether POE scales should be used to evaluate biophilic design evaluation.
| null | null |
buildings12040417_perova
| 0 |
Response 6: The different genders and different ages are included in the study.
| null | null |
As mentioned in the Conclusion, in the future study, we will include more offices and locations as experiment samples.
| null | null |
buildings12040417_perova
| 0 |
how satisfied are you with the biophilic features) may not accurately depict every beneficial nuance they offer (e.g.
| null | null |
According to the research objectives of this study (i.e., evaluate the subjective health impacts of biophilic design in workplace), we need to refer the well-developed scales from other disciplinary (e.g., Environmental Psychology).
| null | null |
buildings12040417_perova
| 0 |
25,39], and the 14 patterns of biophilic design [ref.40].
| null | null |
A quantitative study for indoor workplace biophilic design to improve health and productivity performance.
| null | null |
buildings12040417_perova
| 0 |
Perhaps this makes this article completer and more credible.
| null | null |
And the questionnaire can be applied in future biophilic design research for investigation.
| null | null |
buildings12040417_perova
| 0 |
I think psychological factors will also affect human physiological comfort.
| null | null |
across subsets, leading to no significant differences across subsets.
| null | null |
buildings12040417_perova
| 0 |
Dynamic & Diffuse Light Leveraging varying intensities of light and shadow that change over time to create conditions that occur in nature.
| null | null |
The introduction of the term "Biophilia" can be more detailed and easier to understand.
| null | null |
buildings12040417_perova
| 0 |
Revision in Page 13 Line 381-394: The Cronbach’s α coefficient value of the main scale is 0.72, while those of the subscales GH, NR, and BDE in order are obtained as 0.68, 0.79, and 0.63, indicating that the questionnaire is reliable (i.e., an acceptable reliability: Cronbach's α>0.6) [57, 58] (Table 8).
| null | null |
There are general biophilic design frameworks (e.g., the 24 Biophilic Design Attributes and the 14 Patterns of Biophilic Design) and green building, healthy building standards (e.g., WELL v2 and Singapore Green Mark) that include biophilia into the certification systems in nowadays.
| null | null |
buildings12040417_perova
| 0 |
Both classifications validated by previous literatures.
| null | null |
), Innovative Developments in Architecture, Engineering and Construction.
| null | null |
buildings12040417_perova
| 0 |
outside of POE studies) have been adopted for this reason, and a short sentence explaining the rationale supporting the lack of scales for biophilic design could be provided to briefly mentioned this.
| null | null |
More than 60 percent (approximately 60.7%) of respondents believe that greenery is a biophilic design that benefits office wellbeing (BDE6-Q21).
| null | null |
buildings12040417_perova
| 0 |
According to the quantitative results presented in Table 8, the medians (Interquartile Range, IQR) of the assessment show moderately high opinions toward the health and wellbeing of biophilic offices (HWBO), at 71.00 (8.00) (the score range from min. 20 to max. 100).
| null | null |
Point 3: P2, 47-53: Although in the past there were few guidelines, nowadays, there may be more standards that focus on nature integration within the built environment.
| null | null |
buildings12040417_perova
| 0 |
Author Response Point 1: The introduction can be optimized appropriately.
| null | null |
Therefore, the weighting results of this experiment are not employed to deny the ranking in the 14 Patterns of Biophilic Design.
| null | null |
buildings12040417_perova
| 0 |
Hence, the questions in the final section are designed based on the selection of the biophilic design elements/attributes that typically applied in the office design, which are not mentioned in the previous scales.
| null | null |
Revision in Page 6 Line 215-220: “Table 2 made a comparison between the selected nine biophilic design attributes for workplace in this study and the validated eight factors that affect workers’ satisfaction and productivity.
| null | null |
buildings12040417_perova
| 0 |
Further studies could include more offices and locations as experiment samples.
| null | null |
Point 7: Something I felt would useful would at the beginning would be a clear definition for what “biophilic attributes” refers to.
| null | null |
buildings12040417_perova
| 0 |
Point 4: The result of biophilic design frameworks for specific workplace typology is of certain value.
| null | null |
While this is somewhat accurate, it might be more appropriate to elucidate this as an “inherent affinity”.
| null | null |
buildings12040417_perova
| 0 |
The Conclusion is rewritten to highlight the contribution and implementation of the results: Revision in Page 23 Line 516-540: “The significant research outputs from the present scrutiny are shown as following: a) The authors develop a POE questionnaire for evaluating the biophilic design for workplace health and wellbeing.
| null | null |
#2: P1, L39-41: Please provide references to these frameworks.
| null | null |
buildings12040417_perova
| 0 |
As mentioned in the Conclusion, in the future study, we will include more offices and locations as experiment samples.
| null | null |
9. material Connection with nature Material and elements from nature that, through minimal processing, reflect the local ecology or geology to create a distinct sense of place.
| null | null |
buildings12040417_perova
| 0 |
Additionally, the effectiveness of such design in practical design projects for user wellbeing still requires confirmation.
| null | null |
Questionnaire Results focus on illustrating the questionnaire results.
| null | null |
buildings12040417_perova
| 0 |
Therefore, the weighting results of this experiment are not employed to deny the ranking in the 14 Patterns of Biophilic Design.
| null | null |
Response 6: The different genders and different ages are included in the study.
| null | null |
buildings12040417_perova
| 0 |
Mollazadeh, M., Zhu, YM., Application of Virtual Environments for Biophilic Design: A Critical Review.
| null | null |
Stacked graph with percentage responses for individually arranged items (from the bottom with a high percentage of disagreement to the top with high percentage of agreement).
| null | null |
buildings12040417_perova
| 0 |
If this was the case, then please better articulate its overarching utility in this study, considering that half of the patterns were not relevant to the research scope.
| null | null |
Response 19: The Conclusion is rewritten to highlight the relationship between biophilic design and occupant health and wellbeing: Revision in Page 23 Line 514-540: “The significant research outputs from the present scrutiny are shown as following: a) The authors develop a POE questionnaire for evaluating the biophilic design for workplace health and wellbeing.
| null | null |
buildings12040417_perova
| 0 |
Observation Results-Biophilic Design Attributes in the Selected Offices is moved to be Section 2.3.2.
| null | null |
Practical methodologies to establish biophilic design frameworks for specific workplace typology.
| null | null |
buildings12040417_perova
| 0 |
Response 5: The sentence was rewritten in the updated version.
| null | null |
Although this I don’t believe this would be a large undertaking, the analysis would be better served by non-parametric tests due to the level of measurement used (i.e.
| null | null |
buildings12040417_perova
| 0 |
Second, the study will provide a new biophilic design guidelines for workplaces, which can effectively assist researchers and designers to improve office biophilic design practices and decision-making on design attributes selection.
| null | null |
#2: P1, L39-41: Please provide references to these frameworks.
| null | null |
buildings12040417_perova
| 0 |
The major scale of the questionnaire consists of three parts (subscales): general health (GH), nature relatedness (NR), and biophilic design evaluation (BDE).
| null | null |
This becomes an issue later, since some aspects referring to biophilic design become unclear.
| null | null |
buildings12040417_perova
| 0 |
That is plenty and a challenge for many, but the other imaging modalities used are either standard fare in many centers (x-ray imaging, endoscopy) or do not need to be in adjacent rooms (PET scanning and angiography (can be done in the primary Or).
| null | null |
As we all know surgery of chordomas, especially of recurrent chordomas, is challenging and the authors should be congratulated for their thoroughly surgical planning and approaches, using elaborate pre- and intraoperative imaging, which is well described throughout the manuscript.
| null | null |
cancers14040966_makarova
| 0 |
All that is needed is easy intra-operative access to CT and MR imaging and the ability to import and reconstruct the data real time.
| null | null |
The authors are to be commended for pursing this approach in a small series of patients with difficult diagnoses.
| null | null |
cancers14040966_makarova
| 0 |
What means Volume reduction 0 and 0% in Table 4?
| null | null |
However, the PET scan does not appear to have actually been used for intraoperative repeat imaging to assess resection, and fluoroscopy and 3D reconstructions using Brain Lab software are standard fare in many operating rooms.
| null | null |
cancers14040966_makarova
| 0 |
There is not much to add and publication can be recommended.
| null | null |
3D reconstructions of newly acquired data is a capability of the software, and is available in many places.
| null | null |
cancers14040966_makarova
| 0 |
Intraoperative angiography might have been used in the case of vascular injury but this also is available in many institutions.
| null | null |
Making this clear is important for others who either use the technique or who want to do so.
| null | null |
cancers14040966_makarova
| 0 |
However, patients’ symptoms, tumour location, surgical approach, imaging, complications and outcome are well documented in the tables, and additionally illustrated by two case reports.
| null | null |
As we all know surgery of chordomas, especially of recurrent chordomas, is challenging and the authors should be congratulated for their thoroughly surgical planning and approaches, using elaborate pre- and intraoperative imaging, which is well described throughout the manuscript.
| null | null |
cancers14040966_perova
| 0 |
Intraoperative angiography might have been used in the case of vascular injury but this also is available in many institutions.
| null | null |
That is plenty and a challenge for many, but the other imaging modalities used are either standard fare in many centers (x-ray imaging, endoscopy) or do not need to be in adjacent rooms (PET scanning and angiography (can be done in the primary Or).
| null | null |
cancers14040966_perova
| 0 |
As we all know surgery of chordomas, especially of recurrent chordomas, is challenging and the authors should be congratulated for their thoroughly surgical planning and approaches, using elaborate pre- and intraoperative imaging, which is well described throughout the manuscript.
| null | null |
That is plenty and a challenge for many, but the other imaging modalities used are either standard fare in many centers (x-ray imaging, endoscopy) or do not need to be in adjacent rooms (PET scanning and angiography (can be done in the primary Or).
| null | null |
cancers14040966_perova
| 0 |
Muliti-modality intraoperative imaging is an important adjunct for the neurosurgeon and in this regard, the paper is valuable.
| null | null |
However, chordoma is a rare disease and reports on large patient series are rare.
| null | null |
cancers14040966_perova
| 0 |
If the journal requires an unstructured abstract instead, please reorganize the current abstract so that the content flows uninterrupted (e.g.
| null | null |
Comments to authors: Major: Based on the cell line RNA and protein data the expression level of MACC1 is highly variable rather than being present or not.
| null | null |
cancers14071773_makarova
| 0 |
The results are interesting and may have clinical relevance.
| null | null |
The concentration used from selumetinib both for the cell line experiments (10 microM) and for the animal experiments (50 mg/kg) are quite high.
| null | null |
cancers14071773_makarova
| 0 |
Based on these comments we herewith respond to all questions raised in a point-by-point manner, as follows: Reviewer 1: 1.
| null | null |
[2] Abstract says 266 patients were analyzed (line 36), while result says 360 patients were analyzed (line 249).
| null | null |
cancers14071773_makarova
| 0 |
In this paper the authors represents that MACC1 is a negative prognostic marker in esophageal and gastric adenocarcinomas in a large Caucasian cohort.
| null | null |
The authors argue that MACC1 expression did not significantly influenced cell proliferation in the two cell line models.
| null | null |
cancers14071773_makarova
| 0 |
Author Response Please see the attachment Author Response File: Author Response.pdf
| null | null |
[5] If possible, please use a higher resolution version of Figures 3F and 3I (the legends are blurry and hard to read in the current version).
| null | null |
cancers14071773_makarova
| 0 |
Answer: We thank the reviewer for this comment.
| null | null |
It would be nice to know the selumetinib sensitivity of the two used cell lines.
| null | null |
cancers14071773_makarova
| 0 |
FLO1 EV FLO1 MACC1 0 50 100 150 AUC (72h) Percent of Controll MACC1 related Proliferation over 72h p = 0.113 p=0.113
| null | null |
I recommend the following edits before publication.
| null | null |
cancers14071773_makarova
| 0 |
[3] Throughout the paper, 10^x wrongly displays as 10x (e.g.
| null | null |
The authors´answer regarding the cut off is sufficient, please include this argument either in the methods section or as supplementary information.
| null | null |
cancers14071773_makarova
| 0 |
I recommend the following edits before publication.
| null | null |
In the pdf I reviewed, the caption is there, but the figure is not.
| null | null |
cancers14071773_makarova
| 0 |
[10] If the journal allows it, please break up the abstract into Introduction, Methods, Results, Conclusion.
| null | null |
[7] In line 272/273: (i) please report median survival in each group (instead of mean survival), (ii) please specify Hazard ratio with 95% confidence interval (in addition to p values), (iii) please report both overall survival result and disease-specific survival result (since you showed both in Figures).
| null | null |
cancers14071773_makarova
| 0 |
Please provide the distribution of the IRS scores of the patient cohort and explain how was IRS 5 chosen as cut off?
| null | null |
In order to draw a conclusion about the proliferation effect a longer (48 or 72 hours) measurement is necessary.
| null | null |
cancers14071773_makarova
| 0 |
Please provide the distribution of the IRS scores of the patient cohort and explain how was IRS 5 chosen as cut off?
| null | null |
Please provide the distribution of the IRS scores of the patient cohort and explain how was IRS 5 chosen as cut off?
| null | null |
cancers14071773_makarova
| 0 |
If the journal requires an unstructured abstract instead, please reorganize the current abstract so that the content flows uninterrupted (e.g.
| null | null |
In the pdf I reviewed, the caption is there, but the figure is not.
| null | null |
cancers14071773_makarova
| 0 |
In the pdf I reviewed, the caption is there, but the figure is not.
| null | null |
Dear Professor Mok, We appreciate that you give us the possibility to revise our manuscript and we thank the reviewers again for their valuable comments.
| null | null |
cancers14071773_makarova
| 0 |
They found that MACC1 expression does not influence cell proliferation but is correlated with cell migration.
| null | null |
"MACC1 is an independent negative prognostic marker in AGE/S patients."
| null | null |
cancers14071773_makarova
| 0 |
[7] In line 272/273: (i) please report median survival in each group (instead of mean survival), (ii) please specify Hazard ratio with 95% confidence interval (in addition to p values), (iii) please report both overall survival result and disease-specific survival result (since you showed both in Figures).
| null | null |
Is there a similar variability present among the tissue samples?
| null | null |
cancers14071773_makarova
| 0 |
However, cell proliferation was analyzed only in a 24-hour long period even though most cancer cells have a doubling time around 24 hours.
| null | null |
If the difference is statistically significant, please briefly explain/speculate why.
| null | null |
cancers14071773_perova
| 0 |
FLO1 EV FLO1 MACC1 0 50 100 150 AUC (72h) Percent of Controll MACC1 related Proliferation over 72h p = 0.113 p=0.113
| null | null |
It would be nice to know the selumetinib sensitivity of the two used cell lines.
| null | null |
cancers14071773_perova
| 0 |
Inhibition of MEK1 with selumetinib also reduced cell migration only in MACC1 expressing cells.
| null | null |
They demonstrate that MACC1 is expressed in 79% of the investigated samples and its presence is coupled with reduced overall survival even in patients with good prognosis.
| null | null |
cancers14071773_perova
| 0 |
The results are interesting and may have clinical relevance.
| null | null |
The authors refer to a data "Proliferation of FLO1 EV and FLO1 MACC1 over 72 h", however I couldn´t find the figure either in the manuscript file or here in the answer.
| null | null |
cancers14071773_perova
| 0 |
In the in vitro analysis they investigated MACC1 expression in five cell lines and generated a cell line with MACC1 overexpression and a MACC1 knock-down cell line.
| null | null |
In this study, the authors have shown that the same is also true for gastric/esophageal cancer.
| null | null |
cancers14071773_perova
| 0 |
The authors argue that MACC1 expression did not significantly influenced cell proliferation in the two cell line models.
| null | null |
and before "To analyze the role of MACC1 in vitro the cell lines FLO-1 and OE33 were lentivirally manipulated."
| null | null |
cancers14071773_perova
| 0 |
Please discuss how the applied concentrations are related to the clinically used dosage (75 mg administered orally twice https://clinicaltrials.gov/ct2/show/NCT02448290) and why not the more efficient MEK1 inhibitor trametinib was used for the experiments.
| null | null |
However, cell proliferation was analyzed only in a 24-hour long period even though most cancer cells have a doubling time around 24 hours.
| null | null |
cancers14071773_perova
| 0 |
[5] If possible, please use a higher resolution version of Figures 3F and 3I (the legends are blurry and hard to read in the current version).
| null | null |
[9] In line 277-279: (i) please report median survival in each group (instead of mean survival), (ii) please specify Hazard ratio with 95% confidence interval (in addition to p values).
| null | null |
cancers14071773_perova
| 0 |
If the journal requires an unstructured abstract instead, please reorganize the current abstract so that the content flows uninterrupted (e.g.
| null | null |
Answer: We thank the reviewer for this comment.
| null | null |
cancers14071773_perova
| 0 |
[3] Throughout the paper, 10^x wrongly displays as 10x (e.g.
| null | null |
[10] If the journal allows it, please break up the abstract into Introduction, Methods, Results, Conclusion.
| null | null |
cancers14071773_perova
| 0 |
Dear Professor Mok, We appreciate that you give us the possibility to revise our manuscript and we thank the reviewers again for their valuable comments.
| null | null |
Inhibition of MEK1 with selumetinib also reduced cell migration only in MACC1 expressing cells.
| null | null |
cancers14071773_perova
| 0 |
It would be nice to know the selumetinib sensitivity of the two used cell lines.
| null | null |
[10] If the journal allows it, please break up the abstract into Introduction, Methods, Results, Conclusion.
| null | null |
cancers14071773_perova
| 0 |
Author Response Dear Professor Mok, We appreciate that you give us the possibility to revise our manuscript and we thank the reviewers for their valuable comments.
| null | null |
[5] If possible, please use a higher resolution version of Figures 3F and 3I (the legends are blurry and hard to read in the current version).
| null | null |
cancers14071773_perova
| 0 |
In an in vivo xenograft model using a control and a MACC1 overexpressing cell line pair they found that MACC1 expression increased metastasis formation and this was reduced by selumetinib treatment.
| null | null |
The authors argue that MACC1 expression did not significantly influenced cell proliferation in the two cell line models.
| null | null |
cancers14071773_perova
| 0 |
In order to draw a conclusion about the proliferation effect a longer (48 or 72 hours) measurement is necessary.
| null | null |
[5] If possible, please use a higher resolution version of Figures 3F and 3I (the legends are blurry and hard to read in the current version).
| null | null |
cancers14071773_perova
| 0 |
Please discuss how the applied concentrations are related to the clinically used dosage (75 mg administered orally twice https://clinicaltrials.gov/ct2/show/NCT02448290) and why not the more efficient MEK1 inhibitor trametinib was used for the experiments.
| null | null |
The authors argue that MACC1 expression did not significantly influenced cell proliferation in the two cell line models.
| null | null |
cancers14071773_perova
| 0 |
The materials and methods section are elaborated in the details.
| null | null |
ANOVA = analysis of variance; HCC = hepatocellular carcinoma; RMS = root mean square; SEM = standard error of the mean; TTFields = Tumor Treating Fields.
| null | null |
cancers14122959_makarova
| 0 |
Is that timing enough to get protein expression?
| null | null |
The manuscript is an interesting work related to a potential new therapy of hepatocellular carcinoma (HCC) by using TTFields in combination with a TKI (Sorafenib).
| null | null |
cancers14122959_makarova
| 0 |
In this manuscript, the authors, Davidi et al have investigated the effect of TTFields in HCC cells and an animal model, alone or in combination with sorafenib.
| null | null |
Maybe the cytotoxicity data will reveal a different better frequency.
| null | null |
cancers14122959_makarova
| 0 |
Concomitant TTFields with Sorafenib Enhances Treatment Efficacy in Vivo: “Tumor histology and immunostaining for beclin-1 and LC3, GRP78, and cleaved PARP were performed to examine autophagy, ER stress, and apoptosis levels, respectively.
| null | null |
Similarly, low evidence of apoptosis (expression of cleaved PARP) was found in these groups, as shown in Figure 4F.
| null | null |
cancers14122959_makarova
| 0 |
*p < 0.05 relative to control; one-way ANOVA.
| null | null |
Concomitant TTFields with Sorafenib Enhances Treatment Efficacy in Vivo: “Tumor histology and immunostaining for beclin-1 and LC3, GRP78, and cleaved PARP were performed to examine autophagy, ER stress, and apoptosis levels, respectively.
| null | null |
cancers14122959_makarova
| 0 |
When compared with sorafenib alone there is practically no difference.
| null | null |
Moreover, in the Discussion section, the authors concluded that “TTFields display efficacy for treatment of HCC in vitro and in vivo, with an optimal frequency of 150 kHz”.
| null | null |
cancers14122959_makarova
| 0 |
However, the limited experimental design and paucity of strong data ask for more experiments to proof the feasibility of this combination for treating HCC.
| null | null |
*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 relative to time-respective control; two-way ANOVA.
| null | null |
cancers14122959_makarova
| 0 |
ANOVA = analysis of variance; HCC = hepatocellular carcinoma; RMS = root mean square; SEM = standard error of the mean; TTFields = Tumor Treating Fields.
| null | null |
GRP78 levels in the groups treated with TTFields or sorafenib alone remained unchanged from the control, but were elevated 2-fold in the TTFields plus sorafenib group (Figure 4f).
| null | null |
cancers14122959_makarova
| 0 |
Similarly, low evidence of apoptosis (expression of cleaved PARP) was found in these groups, as shown in Figure 4F.
| null | null |
Point 1: What is the rationale of using 150 kHz TTFields?
| null | null |
cancers14122959_makarova
| 0 |
Overall, the authors believe that this research demonstrates potential for concomitant TTFields and sorafenib application in the treatment of HCC.
| null | null |
While I do not know if the authors have the technology to perform TTFields in mice, where for sure they should have done xenograft models with the two human cell lines, why the rat cell line was not studied in vitro using the same experimental strategies as for human cells.
| null | null |
cancers14122959_makarova
| 0 |
Also, is there any evidence that TTF may prevent the pretty common resistance to sorafenib observed in clinic?
| null | null |
Since the authors missed to add Figure 4A for timeline, based on Methods section the rats were treated for 5 days with TTFields and or sorafenib and a day later the rats were sacrificed.
| null | null |
cancers14122959_makarova
| 0 |
Response to Reviewer 1 Comments In this manuscript, the authors, Davidi et al have investigated the effect of TTFields in HCC cells and an animal model, alone or in combination with sorafenib.
| null | null |
Point 2: Despite the expression of cleaved PARP was very low in the tumors treated with TTFields or sorafenib alone (as shown in IHC-images in Figure 4F), the authors declare about ~ 20% of positive cells, as show in the graphs below IHC-staining.
| null | null |
cancers14122959_makarova
| 0 |
Response 5: We thank the reviewer for this question.
| null | null |
In this manuscript, the authors, Davidi et al have investigated the effect of TTFields in HCC cells and an animal model, alone or in combination with sorafenib.
| null | null |
cancers14122959_makarova
| 0 |
Point 4: Since Annexin V/7-ADD data was not convincing and the authors observed the minor increase of apoptotic cells after HCC cells were treated with combination of TTFields and sorafenib (when compared to the cells treated with TTFields and sorafenib alone), I suggest to run the WBs to examine the expression of the cleaved forms of PARP and caspase-3 (for both HCC cell lines).
| null | null |
Several data have shown very high error bars in each group (especially Fig Can the author provide the tumor images which were harvested from mice?
| null | null |
cancers14122959_makarova
| 0 |
Similar, the graphs illustrating the LC3 expression are not in a proper fit with the images shown in Figure 4D.
| null | null |
Response to Reviewer 1 Comments In this manuscript, the authors, Davidi et al have investigated the effect of TTFields in HCC cells and an animal model, alone or in combination with sorafenib.
| null | null |
cancers14122959_makarova
| 0 |
Response 6: We thank the reviewer for this comment.
| null | null |
I read the manuscript with interest and commend the authors for the work done in the area of liver cancer treatment.
| null | null |
cancers14122959_makarova
| 0 |
Concomitant TTFields with Sorafenib Enhances Treatment Efficacy in Vivo: “Tumor histology and immunostaining for beclin-1 and LC3, GRP78, and cleaved PARP were performed to examine autophagy, ER stress, and apoptosis levels, respectively.
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Moreover, there is a discrepancy between the fold changes in tumor weight vs. volume in the combination group vs. untreated group.
| null | null |
cancers14122959_makarova
| 0 |
Author Response Please see attachment Author Response File: Author Response.docx
| null | null |
Why did the authors use high frequency of TTFields though the cytotoxicity was also observed in lower dose (Fig 1A).
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cancers14122959_makarova
| 0 |
There is a big difference between a therapy which kills vs a therapy which induces a cellular arrest.
| null | null |
Therefore, I expect further additional examination in the future.
| null | null |
cancers14122959_makarova
| 0 |
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