2020-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/671241雖然臨床上，大多數甲狀腺癌是低惡性度之內分泌腫瘤，但大多數患者通常接受放射性碘-131之治療及甲狀腺切除術。此類患者在術後以甲狀腺超音波檢查和連續血清甲狀腺球蛋白評估進行追蹤。以前的研究顯示，三分之一的分化良好的甲狀腺癌可能在疾病進展中轉化為分化不良的模式，甚至是致命的惡性腫瘤，但手術、化學治療及體外放射線治療的療效，成效並不顯著。也就是說，有效的治療策略及追蹤模式是非常重要的，包括手術切除甲狀腺癌，放射碘-131治療，以及甲狀腺腫瘤指標之追蹤。甲狀腺癌細胞分化不良時，細胞去分化是惡性轉化和侵襲的關鍵因素。通常在甲狀腺乳頭狀癌和甲狀腺濾泡癌時，癌細胞會逐漸發生去分化現象，而甲狀腺未分化癌是最後的結果。因此，我們嘗試通過尿液中的外泌體蛋白質表現，來尋找生物標記和治療追蹤的標的，本項臨床研究的基礎在於先前甲狀腺未分化癌細胞培養基礎實驗。外泌體是分泌到細胞外環境中的奈米小體。可以在癌症患者的血漿，唾液，尿液和其他體液中發現癌細胞衍生的外泌體。我們將分析尿液中之外泌體蛋白質，包括甲狀腺球蛋白和半乳凝素-3，通過前瞻性研究發現尿中早期預後生物標誌物。我們過去已經收集20位甲狀腺乳突癌、濾泡癌或未分化癌之患者，在手術前及術後進行進一步治療時，在術前，以及術後、術後3個月、6個月不同階段尿液進行尿液中之細胞外泌體(Exosome)生物標記分析，並找出甲狀腺癌術後及做完碘-131放射治療病人的尿液中細胞外泌體(Exosome)中的特定蛋白質，可能可作為預後追蹤的指標。論文已撰寫，並在國外期刊審查中。本項前瞻性追蹤研究，預計收集150位甲狀腺乳突癌、濾泡癌或未分化癌之患者，已經甲狀腺切除術，並完成根除治療後，於門診追蹤時留取尿液，每年追蹤，連續三年，進行尿液中外泌體 (Exosome)生物標記分析，期望以此前瞻性之研究，找出未來病患預後因子，並發展新穎之甲狀腺癌術後追蹤模式。Although thyroid cancers are low-grade endocrine malignancy, most patients usually received thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Prior researches indicated that one-third well-differentiated thyroid cancers could transform to poorly-differentiated patterns, even to be anaplastic thyroid cancer (ATC), a fatal malignancy, and no effective therapeutic strategies was noted, including surgical intervention, chemotherapy and radiotherapy. The poorly-differentiated or anaplstic change of thyroid cancer cells proliferates rapidly and always invades local tissues with distant metastasis. Cellular de-differentiation is the most pivotal cause for malignant transformation and invasion. De-differentiation usually in papillary thyroid cancer and follicular thyroid cancer, and definitely in ATC. Therefore, we try to find the biological markers and therapeutic targets via the exosomal expression in urine. On the continuing basis of prior ATC cells culture experiments. Exosomes are nanovesicles secreted into extracellular environments. Cancer cell-derived exosomes could be found in plasma, saliva, urine and other body fluid of patients with cancer. We try to analyze the urinary exosomal proteins, including thyroglobulin and galectin-3, to find the early prognostic biological markers in urine via this prospective study We expected to enroll 150 post-operative patients with papillary, follicular or anaplastic thyroid cancer, and collect their urine samples in outpatient clinic per year for at least three consecutive years. We will analyze the urine exosomal proteins and probable biological markers, including thyroglobulin and galectin-3. We hope to find the prognostic biological markers via this prospective study. We further hope to find newly therapeutic and follow-up pathway for such patients with well-differentiated or anaplastic thyroid cancer.