- 作者列表："Thammaroj P","Chimcherd A","Chowchuen P","Panitchote A","Sumananont C","Wongsurawat N
PURPOSE:Cholangiocarcinoma (CCA) is the second most common primary malignant hepatic tumor originating from bile duct epithelia. Bone metastasis is uncommon and less documented. The aim of this study was to characterize the imaging features of bone metastasis from CCA. METHODS:A retrospective descriptive imaging characteristics in 199 patients (1465 lesions) diagnosed as CCA with bone metastasis were evaluated based on plain radiography, computed tomography (CT), magnetic resonance imaging (MRI) and Tc-99 m methylene diphosphonate bone scan. RESULTS:The common vertebral metastatic sites were lumbar spines (94 [47.2 %], 95 %CI 40.1-54.4), upper thoracic spines (89 patients [44.7 %], 95 % CI 37.7-51.9), and lower thoracic spines (80 [40.2 %], 95 % CI 33.3-47.4). On plain radiograph, most of lesions had osteolytic pattern (68 %) with pedicular destruction (45.3 %) whereas on CT had mixed osteolytic and osteosclerotic destruction (40.8 %). The common non-vertebral metastatic sites were ribs and pelvis (80 patients [40.2 %], 95 % CI 33.3-47.4 and 60 [30.2 %], 95 % CI 23.9-37). On plain radiograph, in the long bones, usually had permeative destruction (58.9 %), whereas on CT showed mixed osteolytic and osteosclerotic (34.6 %). On bone scan, increased-uptake was the common pattern, found in the vertebral and non-vertebral sites (93.6 % and 92.4 %). CONCLUSIONS:Bone metastasis from CCA usually occurred in the axial skeleton. The common patterns of destruction were osteolytic or mixed osteolytic and osteosclerotic. Periosteal reaction was scant in the appendicular long bones. On bone scan commonly had increased-uptake.
目的: 胆管癌 (CCA) 是起源于胆管上皮的第二大原发性肝脏恶性肿瘤。骨转移是罕见的，较少记录。本研究的目的是描述 CCA 骨转移的影像学特征。 方法: 回顾性分析 199 例 (1465 个病灶) 经 x线平片、计算机断层扫描 (CT) 、磁共振成像 (MRI) 诊断为 CCA 骨转移患者的影像学特征。并 Tc-99 亚甲基二膦酸盐骨扫描。 结果: 常见的椎体转移部位为腰椎 (94 [47.2%]，95% CI 40.1-54.4)，上胸椎 (89 例 [44.7%], 95% CI 37.7-51.9) 和下胸椎棘 (80 [40.2%]，95% CI 33.3-47.4)。平片上多数病灶为溶骨型 (68%) 伴椎弓根破坏 (45.3%)，CT 上表现为溶骨和骨硬化性混合破坏 (40.8%)。常见的非椎体转移部位为肋骨和骨盆 (80 例患者 [40.2%]，95% CI 33.3-47.4 和 60 [30.2%]，95% CI 23.9-37)。平片上，长骨通常有渗透性破坏 (58.9%)，而 CT 上显示混合溶骨和骨硬化 (34.6%)。在骨扫描中，摄取增加是常见的模式，见于椎体和非椎体部位 (93.6% 和 92.4%)。 结论: CCA 骨转移多发生于中轴骨骼。常见的破坏方式为溶骨或混合溶骨和骨硬化。阑尾长骨骨膜反应很少。骨扫描通常有摄取增加。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.