{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T03:26:09Z","timestamp":1783049169880,"version":"3.54.6"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science Research and Innovation Fundamental Fund Fiscal Year 2023"},{"DOI":"10.13039\/501100005790","name":"Thammasat University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005790","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","award":["N42A671041"],"award-info":[{"award-number":["N42A671041"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is one of the most aggressive cancers with a poor prognosis. Current treatment strategies involve hepatobiliary surgery, chemotherapy, radiotherapy, and supportive care; however, the success of these treatments remains limited. Therefore, this study investigated the potential of <jats:italic>Atractylodes lancea<\/jats:italic> (Thunb) D.C. (AL) in limiting the progress of CCA by targeting the expression of cancer-related genes involved in immune responses and circulating tumor cells. The study was part of Phase 2A clinical trial in advanced-stage intrahepatic iCCA (iCCA) patients: Group 1 (n\u2009=\u200916) received low-dose AL (capsule formulation of the standardized extract of AL: CMC-AL) with standard supportive care, Group 2 (n\u2009=\u200916) received high-dose AL with standard supportive care, and Group 3 (n\u2009=\u200916) received standard supportive care alone. Venous whole blood samples (EDTA, 5\u2009ml) were collected from each patient on Day 1 and Day 90 and the non-CCA subjects (n\u2009=\u200916) on Day 1. Fifty-nine samples (48 and 11 samples for Day 1 and Day 90, respectively) were processed for total RNA isolation. Gene expression was evaluated using reverse transcription followed by a PCR array. Regardless of dosage, gene expression patterns in the AL-treated groups closely resembled those of the healthy subjects. Specifically, cancer-associated genes, including <jats:italic>VEGF-A<\/jats:italic>, <jats:italic>NR4A3<\/jats:italic>, <jats:italic>Ki-67<\/jats:italic>, and <jats:italic>EpCAM<\/jats:italic>, were significantly down-regulated. Additionally, the expression levels of immune-related genes were modulated in AL-treated patients. The treatment groups exhibited lower levels of the pro-inflammatory cytokine <jats:italic>IL-6<\/jats:italic>, increased expression of the anti-inflammatory cytokine <jats:italic>IL-10,<\/jats:italic> and cell-mediated immune-related molecules such as <jats:italic>CTLA4<\/jats:italic> and <jats:italic>PFR1<\/jats:italic>. These findings suggest the potential of AL for iCCA treatment. However, additional studies are required to confirm the correlation between gene and protein expression profiles, as well as CTCs profile.<\/jats:p>","DOI":"10.1371\/journal.pone.0323732","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T17:22:02Z","timestamp":1747156922000},"page":"e0323732","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting tumor-associated genes, immune response, and circulating tumor cells in intrahepatic cholangiocarcinoma: Therapeutic potential of Atractylodes lancea (Thunb.) 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