In recent years, the three‐dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo. This system offers several advantages, including high throughput, efficiency, and retention of tumor heterogeneity. Traditional Matrigel‐submerged organoid cultures primarily support the long‐term proliferation of epithelial cells. One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types, either in dual, triple or even multiple combinations. Another solution is a holistic approach including patient‐derived tumor fragments, air‐liquid interface, suspension 3D culture, and microfluidic tumor‐on‐chip models. Organoid co‐culture models have also gained popularity for studying the tumor microenvironment, evaluating tumor immunotherapy, identifying predictive biomarkers, screening for effective drugs, and modeling infections. By leveraging these 3D culture systems, it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Honglin Guo1, *, Weigen Zeng2, *, Lin Feng1, Xuexin Yu3, Ping Li1, Kaitai Zhang1, Zhixiang Zhou4 and Shujun Cheng1 1State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China 2Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China 3College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China 4Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China *These authors contributed to the work equally and should be regarded as co-first authors Correspondence to: Zhixiang Zhou, email: zhzhxpumc@163.com Kaitai Zhang, email: zhangkt@cicams.ac.cn Shujun Cheng, email: chengshj@cae.cn Keywords: field cancerization, CRC, fatty acid metabolism, ribosome biogenesis, CPT2 Received: March 01, 2017 Accepted: April 07, 2017 Published: May 15, 2017 ABSTRACT Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients. Significantly differentially expressed genes related to the distance from the tumor were screened by linear mixed effects analysis using the lme4 package in R. The distance-related differentially expressed genes that were gradually up-regulated (n=302) or gradually down-regulated (n=568) from normal tissues to the tumor were used to construct protein-protein interaction (PPI) networks. Three subnetworks among the gradually up-regulated genes and four subnetworks among the gradually down-regulated genes were identified using the MCODE plugin in the Cytoscape software program. The most significantly enriched Gene Ontology (GO) biological process terms were “ribosome biogenesis”, “mRNA splicing via spliceosome”, and “positive regulation of leukocyte migration” for the gradually up-regulated subnetworks and “cellular calcium ion homeostasis”, “cell separation after cytokinesis”, “cell junction assembly”, and “fatty acid metabolic process” for the gradually down-regulated subnetworks. Combined with the previously constructed multistep carcinogenesis model used for the analysis, 50.59% of the genes in the subnetworks (43/85) displayed identical changes in expression from normal colon tissues to adenoma and colon cancer. We focused on the 7 genes associated with fatty acid metabolic processes in the distance-related down-regulated subnetwork. Survival analysis of patients in the CRC dataset from The Cancer Genome Atlas (TCGA) revealed that higher expression of these 7 genes, especially CPT2, ACAA2 and ACADM, was associated with better prognosis (p = 0.034, p = 0.00058, p = 0.039, p = 0.04). Cox proportional hazards regression analysis revealed that CPT2 was an independent prognostic factor (p = 0.004131). Our results demonstrate that field cancerization occurs in CRC and affects gene expression in normal tissues extending from the tumor, which may provide new insights into CRC oncogenesis and patient progression.

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

BACKGROUND: Early diagnosis and treatment are key to the long-term survival of lung cancer patients. Although CT has significantly contributed to the early diagnosis of lung cancer, there are still consequences of excessive or delayed treatment. By improving the sensitivity and specificity of circulating tumor cell (CTC) detection, a solution was proposed for differentiating benign from malignant pulmonary nodules. METHODS: In this study, we used telomerase reverse transcriptase–based (TERT-based) CTC detection (TBCD) to distinguish benign from malignant pulmonary nodules < 2 cm and compared this method with the pathological diagnosis as the gold standard. FlowSight and FISH were used to confirm the CTCs detected by TBCD. RESULTS: Our results suggest that CTCs based on TBCD can be used as independent biomarkers to distinguish benign from malignant nodules and are significantly superior to serum tumor markers. When the detection threshold was 1, the detection sensitivity and specificity of CTC diagnosis were 0.854 and 0.839, respectively. For pulmonary nodules ≤ 1 cm and 1–2 cm, the sensitivity and specificity of CTCs were both higher than 77%. Additionally, the diagnostic ability of CTC-assisted CT was compared by CT detection. The results show that CT combined with CTCs could significantly improve the differentiation ability of benign and malignant nodules in lung nodules < 2 cm and that the sensitivity and specificity could reach 0.899 and 0.839, respectively. CONCLUSION: TBCD can effectively diagnose pulmonary nodules and be used as an effective auxiliary diagnostic scheme for CT diagnosis. FUNDING: National Key Research and Development Project grant nos. 2019YFC1315700 and 2017YFC1308702, CAMS Initiative for Innovative Medicine grant no. 2017-I2M-1-005, and National Natural Science Foundation of China grant no. 81472013.

Genome-wide expression profiling during development provides useful information to uncover the potential molecular mechanisms of development in mammals. Recent studies have revealed that a subset of lncRNAs can regulate major biological processes during development. Here, we sequenced four tissues, including brain, colon, liver and lung, using RNA-seq across three developmental stages (early, middle and late stage), and then constructed genome-wide expression profiles during macaque development. In each tissue, we identified developmental time-specific lncRNA and mRNA clusters that displayed diverse expression alteration patterns, including a gradual increase, a gradual decrease, or a reversal of expression. These lncRNAs showed more specific functional associations with their corresponding tissues relative to the developmental time-specific mRNAs. Furthermore, we identified 20 spatiotemporal-specific co-modules including 101 lncRNAs and 609 mRNAs distributed at different developmental stages in different tissues. Our findings suggested that lncRNAs could play critical roles in the development of macaques through close cooperation with mRNAs. Finally, we predicted the functions of the spatiotemporal-specific lncRNAs by their spatiotemporal cooperation with mRNAs and further validated our findings using gene knockdown data of mouse. Our study reveals the spatiotemporal characteristics of lncRNAs and provides a functional map of the spatiotemporal-specific lncRNAs during the development of macaques.