Pharmacological evaluation and mechanistic study of compound Xishu Granule in hepatocellular carcinoma

ObjectiveIn this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.MethodsThe effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.ResultsCXG suppressed HepG2 cell proliferation in a time- and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations (P < .01). Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase. Western blotting results showed that Bax was significantly up-regulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration, which increased the Bax/Bcl-2 ratio. PLK1, CDC25C, CDK1, and Cyclin B1 expression were up-regulated. CXG had a good inhibitory effect on graft tumor growth in vivo.ConclusionCXG has good anti-tumor effects in vitro and in vivo. In vitro, CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest. In vivo, CXG significantly inhibited graft tumor growth. The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression, leading to mitotic catastrophe and apoptosis.     

Pulmonary Carcinosarcoma: A Surveillance,Epidemiology, and End Results (SEER) Analysis

IntroductionPulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.Patients and MethodsSEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.ResultsA total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).ConclusionTreatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.     

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。     

Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography

We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ?=?0.903 (p < 0.0001), sensitivity?=?91% and specificity?=?100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.     

Syringocystadenocarcinoma papilliferum associated with atypical stroma: A hitherto undocumented variant of sarcomatoid carcinoma

Carcinosarcomas are biphasic tumors composed of admixed malignant epithelial and mesenchymal components. Numerous terms have been used to name such neoplasms; therefore, terminological confusion is frequent. Most examples of carcinosarcomas are encountered in non‐cutaneous sites, with approximately 100 cases of cutaneous carcinosarcomas reported so far in the English literature. Although different theories have been suggested to explain the occurrence of these peculiar neoplasms, histogenetic mechanisms should be better hypothesized depending on each individual case. Even though prognosis tends to be related to the specific components of the lesion, especially the epithelial one, it seems that cases of cutaneous localization usually have a better outcome. We report an exceedingly rare case of syringocystadenocarcinoma papilliferum which showed an atypical stroma with sarcomatoid appearance, and highlight that the terminology used for this spectrum of lesions is disorganized and confusing.     

Disparity in the use of adjuvant radioactive iodine ablation among high-risk papillary thyroid cancer patients

BackgroundWe sought to identify treatment disparities existing prior to publication of the 2015 American Thyroid Association Management Guidelines in order to identify patients with papillary thyroid cancer (PTC) at risk for receiving inadequate treatment.MethodsPatients diagnosed with PTC from 2011 to 2013 were identified using Surveillance, Epidemiology and End Results database. High-risk disease was defined as T4, N1, or M1. Chi-square tests compared characteristics of patients with and without high-risk disease and characteristics of high-risk patients who did and did not receive radioactive iodine ablation (RAI). Likelihoods of having high-risk disease, of receiving RAI, and of cause-specific death were calculated using regression analyses.ResultsSample included 32,229 individuals; 7894 (24.5%) had high-risk disease. Mean age was 50.0 years, 24,815 (77.0%) were female, and 21,318 (66.2%) were white. Odds of high-risk disease were greater among males (OR:2.04; 95% CI:1.92–2.16), Hispanics (OR:1.67; 95% CI:1.56–1.79) and Asians (OR:1.49; 95% CI:1.37–1.62), and uninsured (OR:1.24; 95% CI:1.07–1.43), and lower among patients ages 45–64 (OR:0.57; 95% CI:0.53–0.60), and ≥65 years (OR:0.54; 95% CI:0.50–0.59), and Blacks (OR:0.46; 95% CI:0.40–0.53). Most (69.3%) high-risk patients received RAI. Odds of receiving RAI were lower among patients age ≥65 years (OR:0.67; 95% CI:0.58–0.77), uninsured (OR:0.52; 95% CI:0.41–0.67), or with Medicaid (OR:0.58; 95% CI:0.50–0.69). RAI use reduced the risk of cause-specific mortality (HR:0.29; 95% CI:0.18–0.47).ConclusionKnowledge of these treatment disparities will allow recognition of groups at risk for high-risk disease and receiving inadequate treatment.