AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2578-8868/326
1Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre, 191014, Mayakovskogo st., 12, Saint-Petersburg, Russia.
2Federal State budgetary Educational Institution of Higher Education «St. Petersburg State Pediatric Medical University», 194100, Litovskaya st., 2, Saint-Petersburg, Russia.
3Almazov National Medical Research Centre, 197341, Accuratova st., 2, Saint-Petersburg, Russia.4The North-Western State Medical University named after I.I. Mechnikov, 191015, Kirochnaia st., 41, Saint-Petersburg, Russia.
*Corresponding Author: Darya Sitovskaya, Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre, 191014, Mayakovskogo st., 12, Saint-Petersburg, Russia.
Citation: Sitovskaya D.A., Naumova A.D., Sokolova T.V., Krapivin M.I., and Dinikina Yu.V, et al, (2024), Features of Vascular Endothelial Growth Factor А (Vegf-А) Expression in Atypical Teratoid-Rhabdoid Tumor of the Central Nervous System in Children, J. Neuroscience and Neurological Surgery, 14(5); DOI:10.31579/2578-8868/326
Copyright: ©, 2024, Darya Sitovskaya. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Received: 20 June 2024 | Accepted: 08 July 2024 | Published: 22 July 2024
Keywords: atypical teratoid/rhabdoid tumor; AT/RT; VEGF; children; tumors of the central nervous system
Atypical teratoid rhabdoid tumors (AT/RT) are highly malignant neoplasms composed of poorly differentiated germline cells and a variable number of rhabdoid cells that can differentiate into different cell types. A key diagnostic factor for AT/RT is the absence of nuclear expression of the INI1 protein (SMARCB1 gene product) when tested with an anti-INI1 antibody in an immunohistochemical study. Currently, there is no standard treatment for AT/RT, but treatment approaches have become more aggressive and multimodal. In one study, AT/RT was found to be positive for VEGF. The purpose of our study was to examine the expression of VEGF-A in AT/RT in the central nervous system of children. We analyzed biopsy samples from 6 male patients aged 3 months to 8 years (average age 4.5 years). The level of VEGF-A expression was measured by counting the number of brown pixels in the cytoplasm of tumor cells using the PhotoM program in 1 mm2 of tumor tissue. Immunohistochemistry (IHC) revealed varying levels of cytoplasmic staining with an antibody to VEGF-A in 5 out of 6 patients, with the youngest patient (No. 6) showing staining only in endothelial cells. In conclusion, children with AT/RT exhibit different patterns of VEGF-A expression, potentially dependent on the molecular subgroup. Identifying this marker in these highly aggressive tumors could aid in developing new treatment protocols and determining which patients would benefit most from treatment.
Atypical teratoid rhabdoid tumors (AT/RT) are highly malignant neoplasms composed of poorly differentiated germline cells and a variable number of rhabdoid cells. These tumors have the potential to differentiate along neuroepithelial, epithelial, and mesenchymal lineages. AT/RTs can occur throughout the nervous system, with supratentorial tumors being more common in older adults and infratentorial tumors being more prevalent in children. Localization in the spinal cord is rare [1]. While AT/RTs account for only 1-2% of all central nervous system (CNS) tumors in children, they are relatively common in early childhood, accounting for up to 20% of all malignant CNS tumors in children under 3 years of age [2]. The average age of diagnosis is 16-30 months, with a consistent male predominance. Due to the primitive state of the tumor cells and their multilineage differentiation, the histological and immunohistochemical features of AT/RTs can vary greatly. Cell nests often show positivity for synaptophysin, glial fibrillary acidic protein (GFAP), cytokeratins, epithelial membrane antigen (EMA), and smooth muscle actin (SMA) [3]. A significant diagnostic criterion is the absence of nuclear expression of the INI1 protein with anti-INI1 antibody in the case of AT/RTs, while maintaining internal control. This is observed as a result of mutations in the SMARCB1 gene. A small portion of AT/RTs may retain SMARCB1/INI1 expression but may also contain mutations in SMARCA4 [4]. Currently, there is no standard treatment for AT/RTs [5, 6]. Treatment strategies have evolved towards an aggressive multimodal approach, with an overall trend towards improved outcomes. However, the relative contribution of each method (surgery, high-dose chemotherapy, intrathecal chemotherapy, radiation therapy) is still unclear and may depend on the unique biology of the tumor [4].
A hypoxic environment is known to induce the differentiation of cancer stem cells (CSCs) towards endothelial progenitor cells and mature endothelium, which in turn form new blood vessels within the tumor. Tumors generate abnormal and functionally immature blood vessels due to dysregulated factors in the process of pathological angiogenesis. The progression of a brain tumor is closely related to the formation of new blood vessels. Brain tumor angiogenesis is mediated by the action of many angiogenic factors, including VEGF, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), angiopoietins (Angs), and others [7]. Vascular endothelial growth factor (VEGF, OMIM 192240) is a heparin-binding growth factor specific for vascular endothelial cells that is capable of inducing angiogenesis in vivo. It is the only mitogen that specifically acts on endothelial cells, but it also affects neurogenesis [8]. VEGF has six isoforms (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor) [7]. In the nervous system, VEGF-A directly regulates neuronal migration and axon guidance independent of its role in blood vessels. Additionally, VEGF-A has been proposed to play multiple pleiotropic roles in pathological conditions of the central nervous system, such as malignancies and neurodegeneration. VEGF-A also has new functions that act inside the cell, resulting in its expression in an intracrine manner. Intracellularly localized VEGF becomes an important signaling molecule regulating cell growth, survival, and metabolism [9]. A single study showed that VEGF immunopositivity was observed in 83.3% of cases [10]. Therefore, VEGF expression can serve as a prognostic biomarker and be used to determine treatment regimens for atypical teratoid-rhabdoid tumor of the central nervous system in children.
Purpose of the study
To study the features of VEGF-A expression in atypical teratoid-rhabdoid tumor of the central nervous system in children.
Biopsy samples were obtained from brain fragments of 6 male patients with atypical teratoid rhabdoid tumor, ranging in age from 3 months to 8 years with an average age of 4.5 years, from Polenov Neurosurgical Institute – Branch of Almazov National Medical Research Centre. The samples were collected intraoperatively and fixed in 10% buffered formalin. Standard dehydration and paraffin embedding techniques were used. Histological sections were stained with hematoxylin and eosin, and immunohistochemical (IHC) reactions were performed using antibodies to VEGF-A, as well as diagnostic markers GFAP, SMA, EMA, synaptophysin, and INI1 (antibodies from Dako (USA), EnVision imaging system). Fluorescent in situ hybridization (FISH) was also performed using probes for the MYC and SMARCB1 genes. Histological analysis and microphotography were conducted using a Leica Aperio AT2 scanning microscope and AperioImageScope image manager (Leica Microsystems, USA). The results of the reaction with antibodies to VEGF-A were evaluated by counting the number of pixels of the required color (according to the color passport) in the cytoplasm of tumor cells using PhotoM programs (Russia) and further processed using software in the Python programming language. Endothelial cells stained with anti-VEGF-A antibody were excluded from the study. Statistical analysis was not performed due to the small number of patients. The study was conducted in accordance with the Helsinki Declaration of Human Rights, and all patients (or their representatives) provided informed voluntary consent to participate. Preoperative examinations and surgical treatments were carried out in accordance with the Clinical Guidelines of the Association of Neurosurgeons of Russia 2015.
The histological examination of the resected tumors (Fig. 1a-d) revealed a highly malignant, diffusely growing hypercellular tumor with pronounced cellular-nuclear polymorphism. The main pool of cells consisted of clusters of large cells with abundant eosinophilic and light cytoplasm and an eccentrically located round nucleus. The nuclei showed vesicular chromatin and large basophilic nucleoli. Foci of small, monomorphic, embryonic-like cells were also identified, with scant eosinophilic cytoplasm and hyperchromic round nuclei with granular chromatin. In one patient, the embryonic component of the tumor was predominant. The intercellular matrix was scanty, and the tumor stroma was vascularized with thin-walled capillary-type vessels. Foci of ischemic necrosis, high mitotic activity (up to 3 mitoses in 1 field of view at ×400 magnification), and apoptotic bodies were detected. Immunohistochemical examination revealed loss of staining with the INI1 marker in the nuclei of all tumor cells (Fig. 1c). Additionally, deletion of the SMARCB1 gene was detected in two cases (Fig. 1d).
Figure 1. Histological features of AT/RT and results of diagnostic studies.
a-b – diffuse tumor consisting of large cells with abundant eosinophilic cytoplasm and an eccentrically located round nucleus with vesicular chromatin and large basophilic nucleoli. H&E stain, ×400
c – immunohistochemical reaction with antibody to INI1: loss of staining in the nuclei of tumor cells, staining is preserved in the nuclei of the vascular endothelium, ×400.
d – FISH results with a probe to the SMARCB1 gene. Signals to the KREMEN1 (reference) gene are indicated in red, signals to the SMARCB1 gene are indicated in green. Most cells do not carry a single copy of the SMARCB1 gene, ×630.
In addition, the tumor cells exhibited varying levels of staining with antibodies to synaptophysin (Figure. 2a), EMA (Figure. 2b), GFAP (Figure. 2c), SMA (Figure. 2d), and high molecular weight cytokeratins AE1/AE3. The proliferative activity, as indicated by Ki67 staining, was high with an average of 15-20% and reaching up to 30% in "hot" lesions (Figure. 2e).
Figure 2. Results of immunohistochemical reactions in the studied tumors.
a – IHC with antibodies to synaptophysin, ×200
b – IHC with antibodies to EMA, ×200
c – IHC with antibodies to GFAP, ×200
d – IHC with antibodies to SMA, ×400
e – The level of proliferative activity for Ki67 was 15-20%, in “hot” foci up to 30%, ×400
An immunohistochemical study using an antibody to VEGF-A (Figure. 3) showed cytoplasmic staining of varying severity in 5 out of 6 (83.3%) patients, ranging from dot-like to focal-diffuse. In patient No. 6 (the youngest in the study group, 3 months old), staining was only observed in endothelial cells.
Figure 3. Expression of VEGF-A in AT/RT in children (description in text).
Immunohistochemical reaction, ×400 a-e – patients No. 1-5.
The level of VEGF-A expression, calculated by the number of pixels with a positive reaction in the cytoplasm of cells (symbol units, s.u.) per 1 mm2 of tumor tissue, ranged from 0.014 to 0.454 s.u. (μ = 0.173±0.09). The highest values (0.12-0.45 s.u., μ = 0.29±0.13) were found in a patient with a dominant embryonic component in the histological examination. In patients with a homozygous (biallelic) deletion of the SMARCB1 gene (22q11), the level of VEGF-A expression was relatively low, ranging from 0.115 to 0.283 s.u. (μ = 0.19±0.06) and 0.014 to 0.199 s.u. (μn = 0.07±0.06), respectively (Table 1).
| Patient | Gender | Age | VEGF-A expression level, s.u. | Mean (μ) ± standard deviation | SMARCB1 gene deletion | MYC gene amplification | |
| From | To | ||||||
| 1 – D. | male | 4,8 | 0,082 | 0,126 | 0,11 ± 0,02 | – | – |
| 2 – S. | male | 7,2 | 0,12 | 0,45 | 0,29 ± 0,13 | – | – |
| 3 – K. | male | 8,1 | 0,12 | 0,28 | 0,19 ± 0,06 | + | – |
| 4 – N. | male | 4,9 | 0,13 | 0,32 | 0,2 ± 0,08 | – | – |
| 5 – A. | male | 1,7 | 0,01 | 0,2 | 0,07 ± 0,06 | + | – |
| 6 – K. | male | 0,3 | 0 | 0 | 0 | – | – |
Table 1. Patients Information, VEGF-A Expression Morphometry Results, and Molecular Genetic Research Findings
Currently, three molecular subtypes of AT/RT have been identified based on gene expression profiles associated with gender and tumor location. These subtypes, AT/RT-MYC, AT/RT-SHH, and AT/RT-TYR, may have prognostic and therapeutic significance [4, 11]. The AT/RT-TYR subgroup is named after the tyrosinase enzyme, which is overexpressed in most AT/RT-TYR cases but not in other AT/RT subgroups or other brain tumors [11]. This enzyme plays a crucial role in the development of the neural tube by catalyzing the synthesis of melanin in melanocytes. The genetically prototypical type of biallelic inactivation of SMARCB1 in the AT/RT-TYR group is the complete or partial loss of one copy of chromosome 22, accompanied by an inactivating mutation in the other allele of SMARCB1. Clinically, patients in this subgroup are typically the youngest, with a median age at diagnosis of 12 months (range 0–108 months) [1]. This subgroup also has the highest proportion of patients under 3 years of age at diagnosis. The AT/RT-SHH subgroup shows overexpression of both sonic hedgehog (SHH) pathway elements and Notch pathway elements, such as GLI2, PTCH1, and BOC or ASCL1, HES1, DTX1 [12]. All SHH pathway marker genes overexpressed in this subset (such as GLI2) are likely to be activated directly or indirectly by loss of SMARCB1 in these tumors. The AT/RT-MYC subgroup is named based on increased expression of the MYC oncogene (it should be noted that the MYCN oncogene is upregulated in the AT/RT-SHH group). The typical genetic pattern that leads to SMARCB1 inactivation in this group of tumors is homozygous extensive loss of SMARCB1. The mean age of patients with AT/RT-MYC is significantly higher than in the other two subgroups [11]. In our study, due to limitations of the method, it was not possible to determine the exact molecular subgroup. However, in patients who, according to clinical and morphological data, most likely belong to the AT/RT-MYC group, lower levels of VEGF-A expression were noted. It should be noted that due to the small sample size, a conclusion cannot be made. Our study also found that the only infant (3 months) had no expression of VEGF-A. These results raise the question for researchers about the need for routine determination of VEGF-A levels in CNS AT/RT, stratification of expression levels, and potential for chemotherapy.
Children with AT/RT have varying patterns of VEGF-A expression within the tumor structure, potentially influenced by the molecular subgroup. The identification of this marker in these highly aggressive tumors could have significant implications for the development of new therapeutic protocols and for determining which patients would benefit most from treatment.
The authors declare no conflict of interest.
The study was performed without external funding.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
