- 作者列表："Lucci A","Hall C","Patel SP","Narendran B","Bauldry JB","Royal R","Karhade M","Upshaw JR","Wargo JA","Glitza IC","Wong MKK","Amaria RN","Tawbi HA","Diab A","Davies MA","Gershenwald JE","Lee JE","Hwu P","Ross MI
PURPOSE:There is a need for sensitive, reproducible biomarkers for stage III melanoma patients to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in melanoma patients; however, there is limited data regarding their significance in stage III disease. The aim of this study was to determine if CTCs are associated with early relapse in stage III melanoma. EXPERIMENTAL DESIGN:We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 stage III melanoma patients. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared between patients with one or more baseline CTC versus those with no CTCs. Log-rank test and Cox regression analysis were applied to establish associations of CTCs with RFS. RESULTS:At least one baseline CTC was identified in 90/243 (37%) patients. Forty-five (19%), 67 (28%), 118 (49%), and 13 (5%) patients were stage IIIA, IIIB, IIIC, or IIID, respectively. CTC detection was not associated with sub stage, or primary tumor characteristics. Multivariable analysis demonstrated that the detection of ≥1 baseline CTC was significantly associated with decreased 6 month RFS (log-rank p <0.0001, hazard ratio (HR) 3.62, 95% confidence interval (CI) 1.78 to 7.36; P <0.0001) and 54 month RFS (log-rank p = 0.01, HR 1.69, CI 1.13 to 2.54; P = 0.01). CONCLUSION:≥1 CTC was independently associated with melanoma relapse, suggesting that CTC assessment may be useful to identify patients at risk for relapse who could derive benefit from adjuvant therapy.
目的: 对于III期黑色素瘤患者，需要敏感、可重复的生物标志物来指导临床决策。循环肿瘤细胞 (CTCs) 可以在黑色素瘤患者中检测到; 然而，关于其在III期疾病中的意义的数据有限。本研究的目的是确定CTCs是否与III期黑色素瘤早期复发相关。 实验设计: 我们前瞻性评估了 243 例III期黑色素瘤患者在临床首次就诊时 (基线) 的CTCs。使用CellSearch系统测量CTCs。比较了一个或多个基线CTC与无CTC患者的无复发生存期 (RFS)。应用Log-rank检验和Cox回归分析建立CTCs与RFS的相关性。 结果: 在 90/243 例 (37%) 患者中发现至少一个基线CTC。IIIA、IIIB、IIIC或IIID期患者分别为 45 例 (19%) 、 67 例 (28%) 、 118 例 (49%) 和 13 例 (5%)。CTC检测与亚分期或原发肿瘤特征无关。多变量分析表明，检测到 ≥ 1 个基线CTC与降低 6 个月RFS显著相关 (log-rank p <0.0001，风险比 (HR) 3.62，95% 置信区间 (CI) 1.78 比 7.36; P <0.0001) 和 54 个月RFS (log-rank p = 0.01，HR 1.69，CI 1.13 ~ 2.54; P = 0.01)。 结论: ≥ 1 CTC与黑色素瘤复发独立相关，提示CTC评估可能有助于确定有复发风险的患者，这些患者可以从辅助治疗中获益。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.