{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:17:33Z","timestamp":1787753853660,"version":"build-2784847793"},"reference-count":36,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100016355","name":"Xuzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["KC23271"],"award-info":[{"award-number":["KC23271"]}],"id":[{"id":"10.13039\/501100016355","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Given that intrinsic and acquired resistance to cetuximab substantially limits its therapeutic efficacy in head and neck squamous cell carcinoma, we sought to elucidate the role of Ras homolog family member A in mediating cetuximab resistance and delineate the mechanisms in both in vitro and in vivo models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Over 8 months, cetuximab-sensitive parental head and neck squamous cell carcinoma cells were exposed to progressively higher concentrations of cetuximab to develop a cetuximab-resistant head and neck squamous cell carcinoma cell line (HN31-R). Ribonucleic acid sequencing revealed significant upregulation of Ras homolog family member A and Rho-associated protein kinase in resistant cells compared with that in parental cells. The correlation between Ras homolog family member A overexpression and resistance to cetuximab was evaluated using Western blot analysis, immunofluorescence staining, and Cell Counting Kit-8 assays. Epigallocatechin-3-gallate was administered to Ras homolog family member A\u2013overexpressing cells, and its effects on cetuximab sensitivity and tumor growth were evaluated in vitro and in a xenograft mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Elevated Ras homolog family member A expression is significantly associated with resistance to cetuximab. Ras homolog family member A knockdown restored cetuximab sensitivity and significantly reduced tumor growth in nude mice. Epigallocatechin-3-gallate treatment was associated with decreased Ras homolog family member A and Rho-associated protein kinase 2 expression and enhanced cetuximab sensitivity in both in vitro and xenograft models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ras homolog family member A may contribute to the development of cetuximab resistance and could be a candidate therapeutic target for future investigation aimed at improving treatment response in head and neck squamous cell carcinoma. The current findings suggest that modulation of the Ras homolog family member A\u2013Rho-associated protein kinase axis is associated with cetuximab sensitivity in head and neck squamous cell carcinoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261479398","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:14:07Z","timestamp":1787584447000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ras homolog family member A expression is associated with reduced cetuximab sensitivity in head and neck squamous cell carcinoma"],"prefix":"10.1177","volume":"54","author":[{"given":"ChaoRong","family":"Bian","sequence":"first","affiliation":[{"name":"Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University"},{"name":"the Second Affiliated Hospital of Xuzhou Medical University"},{"name":"Central Laboratory, Affiliated Hospital of Xuzhou Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University"},{"name":"Central Laboratory, Affiliated Hospital of Xuzhou Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Shen","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runbang","family":"Wang","sequence":"additional","affiliation":[{"name":"Xuzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Pan","sequence":"additional","affiliation":[{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University"},{"name":"Central Laboratory, Affiliated Hospital of Xuzhou Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-5392","authenticated-orcid":false,"given":"Peng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University"},{"name":"Central Laboratory, Affiliated Hospital of Xuzhou Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_3_3_2","first-page":"507","article-title":"Molecularly targeted agents and immunotherapy for the treatment of head and neck squamous cell cancer (HNSCC)","volume":"21","author":"Azoury SC","year":"2016","unstructured":"Azoury SC, Gilmore RC, Shukla V. 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