The expression and functions of microRNAs in pancreatic adenocarcinoma and hepatocellular carcinoma

Pancreatic adenocarcinoma and hepatocellular carcinoma are devastating human malignancies that are characterized by poor prognosis,late onset,and a lack of known biomarkers.New diagnostic and therapeutic molecular targets are desperately needed to develop novel and effective treatment strategies.MicroRNAs (miRNAs) are an emerging class of molecules with roles in various cellular processes,including growth,survival,and apoptosis.Most importantly,aberrant expression of miRNAs has been implicated in cancer pathogenesis.miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma indicate selective overexpression of oncogenic miRNAs and down-regulation of tumor suppressive miRNAs in these cancers.This review summarizes results from key studies conducted to characterize the miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma and describes the potential mechanisms by which some oncogenic or tumor suppressive miRNAs act.Furthermore,this review outlines novel therapeutic strategies for targeting miRNAs.

2023年ASCO肝胆胰恶性肿瘤治疗进展

2023年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)年会于2023年6月2日至6日在芝加哥召开。本次大会报道了多项肝胆胰恶性肿瘤领域的重磅研究,涵盖晚期系统治疗、局部联合系统治疗和围手术期治疗等。这些结果将改变临床实践,推动肝胆胰恶性肿瘤领域的发展。本文重点介绍大会肝细胞癌(hepatocellular carcinoma,HCC)、胆管恶性肿瘤(biliary tract cancer,BTC)和胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)相关研究结果,探讨当前的治疗热点、问题和未来发展方向。

LINC01140在肝胆胰癌中的低表达及其靶向功能预测

目的:分析LINC01140在肝胆胰癌中的差异表达,探讨其靶向功能,为临床诊治肝胆胰癌提供靶向治疗的新思路。方法:通过微阵列及高通量数据,分析肝胆胰癌中LINC01140的差异表达。利用Kaplan-Meier分析评估高、低表达LINC01140两组间预后差异。利用韦恩图对LINC01140靶向的miRNAs与靶向高表达mRNAs分别与肝胆胰癌差异表达的miRNAs与mRNAs取交集,利用Cytoscape构建LINC01140-miRNA-mRNA调控网络。结果:LINC01140在肝胆胰癌中低表达(P<0.01),其SMD值为-0.47[-0.76,-0.18],且低表达LINC01140患者的预后较差。预测LINC01140调控的hsa-miR-199a-3p、hsa-miR-382-3p、hsa-miR-452-5p及hsa-miR-4677-3p,从而预测273个靶向mRNAs,构建LINC01140-miRNA-mRNA调控网络及富集分析,排在前三位的信号通路分别为Salmonella infection、Focal adhesion及Hippo signaling pathway。结论:LINC01140在肝胆胰癌中发挥抑癌作用,低表达具有较差的预后,可能通过LINC01140-miRNA-mRNA来实现,为肝胆胰癌靶向治疗提供新思路。

Potential of the ellagic acid-derived gut microbiota metabolite–Urolithin A in gastrointestinal protection

Urolithin A(UA)is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria.The physiologically relevant micromolar concentrations of UA,achieved in the plasma and gastrointestinal tract(GI)after consumption of its dietary precursors,have been revealed to offer GI protection.The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects.UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity,including those involved in carcinogen biotransformation and antioxidant defense.The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract.The data presented herein,covering both studies on the pure compound and in vivo generated UA form its natural precursor,support the potential of this metabolite in treatment interventions against GI ailments.

E2F transcription factors and digestive system malignancies:How much do we know?

The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell&#x02019;s fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current &#x02018;&#x02018;Letter to the Editor&#x02019;&#x02019;, we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.

肿瘤相关巨噬细胞与肿瘤干细胞相互调控作用的研究进展

肿瘤干细胞(CSCs)在肿瘤中数量极少,但在肿瘤发生、发展、扩散乃至复发的过程中发挥关键作用。CSCs具有无限的自我更新、多向分化以及在体内诱发肿瘤形成的能力。与此同时,CSCs塑造了适宜自身生存的肿瘤免疫微环境,以支持肿瘤生长。其中,肿瘤相关巨噬细胞(TAMs)作为肿瘤组织中最丰富的免疫细胞,受CSCs募集在肿瘤中累积,并通过直接或间接的方式为CSCs提供信号,增强CSCs的“干性”。本文以肝癌、乳腺癌、胶质瘤和胰腺癌为模型,详细讨论TAMs与CSCs间的相互作用,以期为TAMs介导干预CSCs进行肿瘤免疫治疗提供新思路。