Adiposity may predict survival in patients with advanced stage cancer treated with immunotherapy in phase 1 clinical trials.
在 1 期临床试验中，肥胖可能预测免疫治疗晚期癌症患者的生存期。
- 作者列表："Martini DJ","Kline MR","Liu Y","Shabto JM","Williams MA","Khan AI","Lewis C","Collins H","Akce M","Kissick HT","Carthon BC","Shaib WL","Alese OB","Pillai RN","Steuer CE","Wu CS","Lawson DH","Kudchadkar RR","El-Rayes BF","Ramalingam SS","Owonikoko TK","Harvey RD","Master VA","Bilen MA
BACKGROUND:Body mass index (BMI) is used to define obesity, but it is an imperfect measure of body composition. In the current study, the authors explored the association between types of fat and survival in patients treated with immunotherapy. METHODS:A retrospective analysis of 90 patients who were treated with immunotherapy on phase 1 clinical trials at the Winship Cancer Institute in Atlanta, Georgia, from 2009 through 2017 was performed. Overall survival (OS) and progression-free survival (PFS) were used to measure clinical outcomes. Baseline BMI and radiographic images at the middle of the third lumbar vertebrae were obtained. Fat densities were calculated and converted to indices (subcutaneous fat index [SFI], intermuscular fat index [IFI], and visceral fat index [VFI]) after dividing by height in meters squared. Risk groups were created using recursive partitioning and the regression trees method for SFI and IFI, which were selected by stepwise variable selection among all fat-related variables. The Cox proportional hazards model and Kaplan-Meier method were used for the association with OS and PFS. RESULTS:The majority of patients (59%) were male and diagnosed with melanoma (33%) or gastrointestinal cancers (22%). The median BMI was 27.4 kg/m2 , the median SFI was 62.78, the median IFI was 4.06, and the median VFI was 40.53. Low-risk patients (those with an SFI ≥73) had a significantly longer OS (hazard ratio, 0.20; 95% CI, 0.09-0.46 [P < .001]) and PFS (hazard ratio, 0.38; 95% CI, 0.20-0.72 [P = .003]) compared with patients at intermediate risk (those with an SFI <73 and IFI <3.4) and poor risk (those with an SFI <73 and IFI ≥3.4). The Uno concordance statistics were found to be higher for fat risk groups than BMI in predicting OS (0.603 vs 0.574; P = .581) and PFS (0.602 vs 0.586; P = .71). CONCLUSIONS:Increased BMI, increased SFI, and decreased IFI may be associated with prolonged survival in patients with cancer who are treated with immunotherapy. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.
背景: 身体质量指数 (BMI) 被用来定义肥胖，但它是一种不完善的身体成分测量方法。在目前的研究中，作者探讨了脂肪类型与免疫治疗患者生存率之间的关系。 方法: 对 2009 年至 2017 年在佐治亚州亚特兰大Winship癌症研究所进行的 1 期临床试验中接受免疫治疗的 90 例患者进行回顾性分析。使用总生存期 (OS) 和无进展生存期 (PFS) 来衡量临床结局。获得第三腰椎中部的基线BMI和影像学图像。计算脂肪密度，除以身高 (米平方) 后转换为指数 (皮下脂肪指数 [SFI] 、肌间脂肪指数 [IFI] 和内脏脂肪指数 [VFI])。使用递归划分和SFI和IFI的回归树方法创建风险组，在所有脂肪相关变量中通过逐步变量选择来选择。Cox比例风险模型和Kaplan-Meier法用于与OS和PFS的相关性。 结果: 大多数患者 (59%) 为男性，诊断为黑色素瘤 (33%) 或胃肠道癌 (22%)。中位BMI为 27.4千克kg/m2，中位SFI为 62.78，中位IFI为 4.06，中位VFI为 40.53。低风险患者 (SFI ≥ 73) 的OS显著较长 (风险比，0.20; 95% CI，0.09-0.46 [P < .001]) 和PFS (风险比，0.38; 95% CI，0.20-0.72 [P = .003]) 与中等风险患者相比(SFI <73 和IFI <3.4 的患者) 和风险差 (SFI <73 和IFI ≥ 3.4 的患者)。发现脂肪风险组的Uno一致性统计在预测OS (0.603 vs 0.574; P = .581) 和PFS (0.602 vs 0.586; P = .71) 方面高于BMI。 结论: 在接受免疫治疗的癌症患者中，BMI增加、SFI增加和IFI降低可能与生存期延长有关。需要进一步的研究来阐明肥胖对免疫治疗的宿主免疫应答的影响。
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.