High Body Mass Index and Central Adiposity Is Associated with Increased Risk of Acute Pancreatitis: A Meta-Analysis
- 作者列表："Aune, Dagfinn","Mahamat-Saleh, Yahya","Norat, Teresa","Riboli, Elio
Background Higher body mass index and waist circumference have been associated with increased risk of pancreatitis in several prospective studies; however, the results have not been entirely consistent. Aims We conducted a systematic review and dose-response meta-analysis of prospective studies on adiposity and risk of pancreatitis to clarify this association. Methods PubMed and Embase databases were searched for studies on adiposity and pancreatitis up to January 27, 2020. Prospective studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between adiposity and risk of pancreatitis were included, and summary RRs (95% CIs) were calculated using a random effects model. Results Ten prospective studies with 5129 cases and 1,693,657 participants were included. The summary RR (95% CI) of acute pancreatitis was 1.18 (95% CI: 1.03–1.35, I ^2 = 91%, n = 10 studies) per 5 kg/m^2 increase in BMI and 1.36 (95% CI: 1.29–1.43, I ^2 = 0%, n = 3) per 10 cm increase in waist circumference. There was evidence of a nonlinear association between BMI and acute pancreatitis, p _nonlinearity < 0.0001, with a steeper association at higher levels of BMI, but not for waist circumference, p _nonlinearity = 0.19. Comparing a BMI of 35 with a BMI of 22, there was a 58% increase in the RR and there was a fourfold increase in the RR comparing a waist circumference of 110 cm with 69 cm. There was no evidence of publication bias. Conclusions This meta-analysis suggests that both increasing BMI and waist circumference are associated with a dose-response-related increase in the risk of acute pancreatitis.
背景在一些前瞻性研究中，较高的体重指数和腰围与胰腺炎风险增加相关; 然而，结果并不完全一致。我们对肥胖和胰腺炎风险的前瞻性研究进行了系统综述和剂量-反应荟萃分析，以阐明这一相关性。方法检索PubMed和Embase数据库中截至 2020 年 1 月 27 日有关肥胖和胰腺炎的研究。纳入报告肥胖与胰腺炎风险相关性的校正相对风险 (RR) 估计值和 95% 置信区间 (ci) 的前瞻性研究，并总结RRs (95% ci) 使用随机效应模型计算。结果共纳入 10 项前瞻性研究，5129 例病例，1,693,657 例参与者。急性胰腺炎的汇总RR (95% CI) 为 1.18 (95% CI: 1.03-1.35，I ^ 2 = 91%，n = 10 项研究) BMI每增加 5千克/m ^ 2，腰围每增加 1.36，增加 95% (1.29 CI: 1.43-0%，I ^ 2 = 10厘米，n = 3)。有证据表明BMI和急性胰腺炎之间存在非线性关联，p _ 非线性 <0.0001，在较高水平的BMI时关联更陡峭，但腰围无关，p _ 非线性 = 0.19。BMI为 35 与BMI为 22 相比，RR增加了 58%，RR增加了 4 倍，腰围为 110厘米与 69厘米相比。没有发表偏倚的证据。结论这项荟萃分析表明，BMI和腰围的增加都与急性胰腺炎风险的剂量反应相关增加有关。
METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.
METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
METHODS:PURPOSE:Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS:We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS:Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS:Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.