English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Bladder cancer is the most common type of genitourinary cancer in China, with an estimated 80,500 new cases and 32,900 related deaths in 2015 alone (Chen et al., 2016). Unlike many other cancers, there has been no significant improvement in survival rates for bladder cancer over the last three decades. Specific treatment regimens for bladder cancer and their efficacy vary depending not only on clinical stages, but also on associated risk factors and other personal clinical characteristics. Patients with non-muscle invasive bladder cancer (NMIBC) have a high 5-year recurrence rate of 60%–70% (Berdik, 2017) and those with muscle invasive bladder cancer (MIBC) has a relatively poor prognosis with approximately 65% risk of death within 5-year follow-up (Kamat et al., 2016). Therefore, there is an urgent need to develop models for bladder cancer to screen for rational treatment strategies by personalized medicine to improve the clinical assessment and treatment of bladder cancer. Conditional reprogramming (CR) technique is a transformational method of cell culture that allows rapid and efficient generation of cells from normal and tumor tissues (Jin et al., 2018). Patient-derived cells can grow indefinitely without genetic manipulation (Liu et al., 2012) and has been proven useful in basic and clinical research in many kinds of cancers (Saeed et al., 2017). In previous cases, CR cultures (CRCs) were generated using biopsy or surgery samples collected through invasive approaches. While it might not be easily performed or accepted in some cases. Liquid biopsies have been proven to provide equally accurate and dynamic clinical information and can capture the complex genetic mutations of profiles of primary and metastatic tumors (Karachaliou et al., 2015). Urine is the most convenient source of liquid biopsies and has been extensively explored for clinical diagnosis of bladder cancer by cytology and biomarkers (Di Meo et al., 2017). Therefore, the establishment of primary urine-derived cancer cell models using CR technique might be ideal in clinical practice. We adapted a CR technique to explore the possibility of establishing bladder cancer cells from patients’ tumor tissues and urine samples and applied the cultures for whole exome sequencing (WES) and drug testing (Fig. 1A). All patients were diagnosed as bladder cancer by pathology, detailed information of patients is summarized in Fig. 1B and Table S1. The overall success rate of culturing urine CRCs was 83.3% (50/60), specifically, high grade bladder cancer was 85.4% (41/48) and low grade bladder cancer was 75.0% (9/12) (Fig. 1C). Moreover, we did not observe the bias of success rates of culturing urine CRCs with respect to gender, pathology group, disease status or age from all bladder cancer patients (Fig. S1). We would like to expand our sample size in the future, especially the tumor in situ bladder cancer. For patients with systemic metastasis of recurrent tumors, we are also trying to culture circulating tumor cells. Primary cells isolated from urine and tumor samples both rapidly formed CRC colonies and representative compact spheroids in 3D culture (Fig. S2A). HE staining results showed that the CRCs exhibited obvious tumor cell properties as with their corresponding tumor pathological section (Fig. S2B). To identify the molecular characteristics, we performed IHC staining to determine the expression of three cell type-specific markers (GATA3, P40, and P63) in urine CRCs. The expression of all three markers were high in the urine CRC of patient 2 and two markers were high (P40, P63) in patient 1, which were consistent with their parental tumor tissues (Fig. 1D). Furthermore, Transwell assays in urine CRC showed different migration abilities for each sample. (Fig. S3). We also carried out WES analysis in urine CRCs and compared the results to the corresponding parental tumors. In total, CR cells shared 79.7%–82.6% of their variation profile with primary tumor tissues (Fig. 1E). Similarly, the analysis of the mutation ratio for both patients’ tissues and corresponding urine CRCs confirmed that both single nucleotide variants (SNVs) and insertions and deletions (indels) in the original tissues were well retained during culturing (Fig. 1E). Parts of the landscape of common somatic mutations among paired urine CRCs, tumor CRCs, and tumor tissues for the same patient are shown in Fig. S5. Some common mutations were also found in these three patient-derived tumor tissues, as shown in Fig. S6. We also identified some SNVs that are not represented in the primary

Continuous culture of urine-derived bladder cancer cells for precision medicine