{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T23:02:50Z","timestamp":1782514970396,"version":"3.54.5"},"update-to":[{"DOI":"10.12688\/f1000research.109142.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000}},{"DOI":"10.12688\/f1000research.109142.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000}}],"reference-count":36,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    \u00a0\n                  <\/ns4:p>\n                  <ns4:p>Sorafenib is a standard drug used for advanced hepatocellular carcinoma but is often resistant and toxic. Its combination with epigallo-3-catechin gallate leads to reduced resistance and toxicity but an equally effective anti-angiogenic effect.Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate.<\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    \u00a0\n                  <\/ns4:p>\n                  <ns4:p>We conducted an animal study and double-blind, randomized controlled trials. A total of 25 male Wistar rats (7 weeks old) were randomly divided into four groups, namely Sham (K), Control (O), a combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg\/kg body weight (BW) intraperitoneally for ten weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for two weeks. Subsequently, liver tissues and tumor masses were examined for vascular endothelial growth factor (VEGF) level and microvascular density expression.<\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                  <\/ns4:p>\n                  <ns4:p>There was a significant difference (p=0.007) in the level of VEGF between group X1 (low dose Sorafenib + EGCG) and X2 (Standard dose Sorafenib). However, the differences in VEGF levels of group X1 and X2 compared to group O(Control) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 and X2\u00a0 was not entirely different. Meanwhile, a significant difference (p&lt;0.05) was discovered when both groups were compared with the control group.<\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion:<\/ns4:bold>\n                  <\/ns4:p>\n                  <ns4:p>The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.<\/ns4:p>","DOI":"10.12688\/f1000research.109142.3","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:38:38Z","timestamp":1671619118000},"page":"289","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Anti-angiogenic effect of the combination of low-dose sorafenib and EGCG in HCC-induced Wistar rats"],"prefix":"10.12688","volume":"11","author":[{"given":"Andry","family":"Irawan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Prabowo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignatius","family":"Riwanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahyuni Lukita","family":"Atmodjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref1","first-page":"517-520","article-title":"Hepatocellular carcinoma - United States, 2001-2006.","volume":"59","year":"2010","journal-title":"MMWR Morb. 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U S A."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/11-289\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-289\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-289\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:30:22Z","timestamp":1674448222000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/11-289\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":36,"URL":"https:\/\/doi.org\/10.12688\/f1000research.109142.3","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.142344.r158508","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.142344.r158945","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.142344.r158945","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.142344.r158508","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.142344.r158508, Yefta Moenadjat, Faculty of Medicine, Department of Surgery Cipto Mangunkusumo General Hospital, Universitas Indonesia, Jakarta, Indonesia, 05 Jan 2023, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-response-158508","order":0,"name":"referee-response-158508","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Andry Irawan<\/b>; \n<i>Posted: 14 Jan 2023<\/i>; Thank you for your valuable feedback.","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-comment-9215","order":1,"name":"referee-comment-9215","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.120607.r151185, Andree Kurniawan, Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia, 23 Sep 2022, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/11-289\/v1#referee-response-151185","order":2,"name":"referee-response-151185","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Andry Irawan<\/b>; \n<i>Posted: 08 Nov 2022<\/i>; Dear Dr Andree Kurniawan,  Thank you for allowing us to submit a revised draft of our manuscript titled \n<i>Anti-angiogenic effect of the combination low-dose sorafenib and EGCG in HCC-induced Wistar rats<\/i>. We appreciate the time and effort you have dedicated to providing your valuable feedback on our manuscript. We are grateful to the reviewer for their insightful comments on our paper. We have been able to incorporate changes to reflect most of the suggestions provided by the reviewer. We have highlighted the changes within the manuscript.  Here is a point-by-point response to the reviewer's comments and concerns.  1. In the introduction may be added the recent update in HCC since there are emerging new data about anti angiogenesis and immunotherapy may be added also the role of levantinib. Sorafenib nowadays is not a standard of care for advanced inoperable HCC. Atezo Bev was the standard of care.  \n<b>Author\u2019s comment: <\/b>We have incorporated the additional statement in the second last paragraph of the introduction.  2. Should be added also in the introduction the background rationale for this research since there are several studies about it already.  \n<b>Author\u2019s comment: <\/b>The research rationale has been stated in the 3\n<sup>rd<\/sup> paragraph of the introduction.  3. In the discussion should be added the implication for clinical practice the combination of experimental drugs. What is the implication for translation research from this data?  \n<b>Author\u2019s comment: <\/b>The combination of low-dose Sorafenib with EGCG has a more potential anti-angiogenic effect in liver cancer by reducing VEGF values compared to the single standard-dose Sorafenib. We can advance the research into human, but firstly we need to examine the toxicity effect in animal research.  4. Advice for further basic research should be added, related to the limitations of this study.&nbsp;  \n<b>Author\u2019s comment: <\/b>The advice for further studies has been mentioned in the limitation section of the discussion.  5. In the discussion do not repeat the results, however, compare the results with other studies - similar results or different results?  \n<b>Author\u2019s comment: <\/b>The comparison with other studies has been incorporated in the 4\n<sup>th<\/sup> paragraph of the discussion.  We look forward to hearing from you in due time regarding the submission, responses, further questions, and comments you may have. Thank you.   Sincerely, Andry Irawan","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-comment-8998","order":3,"name":"referee-comment-8998","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Andry Irawan<\/b>; \n<i>Posted: 17 Dec 2022<\/i>; Dear Dr. Yefta Moenadjat,  Thank you for allowing us to submit a revised draft of our manuscript. We have adjusted several texts and sentences based on your highlighted texts. We also attempted to register the experimental study; however, all animal study registries must be submitted before the research is done. We sincerely regret this matter, and our evaluation will be for the following animal study.  We look forward to hearing from you regarding the submission, responses, questions, and comments you may have. Thank you.   Sincerely, Andry Irawan","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-comment-9137","order":4,"name":"referee-comment-9137","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.142344.r158945, Alessandro Granito, Department of Medical and Surgical Sciences, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy, 16 Jan 2023, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-response-158945","order":5,"name":"referee-response-158945","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Andry Irawan<\/b>; \n<i>Posted: 23 Jan 2023<\/i>; Thank you Dr. Granito for reminding us about the effectiveness of Metronomic Capecitabine in the management of HCC. We hope this combination could be useful and safe as an alternative for managing advanced HCC.","URL":"https:\/\/f1000research.com\/articles\/11-289\/v3#referee-comment-9243","order":6,"name":"referee-comment-9243","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":7,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}