scholarly journals A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elise Y. Cai ◽  
Jose Garcia ◽  
Yuzhen Liu ◽  
Funda Vakar-Lopez ◽  
Sonali Arora ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patient ◽  
Growth Dynamics ◽  
Bladder Cancer Patient ◽  
Cancer Therapies ◽  
Patient Derived Xenograft ◽  
Cancer Models ◽  
Parental Tumor ◽  
Muscle Invasive

AbstractBladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies.

scholarly journals MP54-14 CHARACTERIZATION OF HUMAN BLADDER CANCER PATIENT-DERIVED XENOGRAFT IN VIVO AND IN ORGANOIDS

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Hung-Ming Lam ◽  
Yuzhen Liu ◽  
Funda Vakar-Lopez ◽  
Lisha Brown ◽  
Bruce Montgomery ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patient ◽  
Bladder Cancer Patient ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Patient Derived Xenograft

Characterization of human bladder cancer patient-derived xenograft in vivo and in organoids.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 479-479
Author(s):  
Hung-Ming Lam ◽  
Yuzhen Liu ◽  
Funda Vakar-Lopez ◽  
Lisha Brown ◽  
Robert B. Montgomery ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Bladder Cancer ◽  
Proliferation Index ◽  
Bladder Cancer Patient ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Patient Derived Xenograft ◽  
Late Passage

479 Background: To establish and molecularly characterize a human bladder cancer patient-derived xenograft (PDX) in vivo and in an organoid system derived from the PDX for preclinical studies. Methods: Two-mm3 bits of urothelial carcinoma originated from muscle invasive disease excised in cystectomy were implanted subcutaneously into male severe combined immunodeficient mice to establish PDXs. Established PDXs (CoCaB 1) were passaged subcutaneously in SCID mice and histopathology of each passage was compared with the originating tumor. Tumor size was measured weekly by caliper to determine the growth rate of PDXs from early (P1/P2) through late passage (P8/P9). Representative early and late passages were collected for organoid establishment. For both early and late passages, proliferation was assessed by Ki67 in PDXs and organoids, and cell cycle analysis and MTS assay specifically in organoids. RNA sequencing was performed to compare the fidelity of PDX and organoids vs. primary tumor. Results: Histologically, 16 of the 16 (100%) PDXs generated from early through late passage (1-2 tumors per passage) were similar to the original high-grade urothelial carcinoma. In vivo, the latency of PDX establishment decreased upon passage (9 weeks to take in early P1/2 vs. 2 weeks to take in late P8/9) and the growth rate increased upon passage. Concordantly, Ki67 proliferation index increased from 40% in P1 to 95% in P8 and was positively correlated with increasing passage (Spearman R=0.804, p=0.001). Similarly, in organoids, late passage demonstrated a shorter growth doubling time, higher Ki67 proliferation index, and faster progression through cell cycle. Transcriptional analysis showed that the PDX contained 81-92% human transcripts, whereas organoids contained >99% human transcripts. Conclusions: Bladder cancer PDXs histologically represented the originating disease. PDX and organoid systems demonstrated concordant increase in proliferation upon serial passages, suggesting clonal selection may take place in this aggressive tumor type. Despite more mouse stromal content in PDX, PDX and organoid represent two independent model systems with highly similar biological responses that allow therapeutic studies.

Abstract 97: RNA sequencing of bladder cancer patient-derived xenograft models identifies genes associated with chemoresistance

2017 ◽  
Author(s):  
Kelly A. Martin ◽  
Nicholas R. Hum ◽  
Aimy Sebastian ◽  
Deepa K. Murugesh ◽  
Chong-Xian Pan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patient ◽  
Rna Sequencing ◽  
Bladder Cancer Patient ◽  
Patient Derived Xenograft ◽  
Xenograft Models

Surface Labeling with Adhesion Protein FimH Improves Binding of Immunotherapeutic Agent Salmonella Ty21a to the Bladder Epithelium

2020 ◽  
pp. 1-12
Author(s):  
Maroeska J. Burggraaf ◽  
Lisette Waanders ◽  
Mariska Verlaan ◽  
Janneke Maaskant ◽  
Diane Houben ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Bladder Wall ◽  
Bladder Epithelium ◽  
Modest Improvement ◽  
Adhesion Protein ◽  
Survival Experiment ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is the ninth most common cancer in men. 70% of these tumors are classified as non-muscle invasive bladder cancer and those patients receive 6 intravesical instillations with Mycobacterium bovis BCG after transurethral resection. However, 30% of patients show recurrences after treatment and experience severe side effects that often lead to therapy discontinuation. Recently, another vaccine strain, Salmonella enterica typhi Ty21a, demonstrated promising antitumor activity in vivo. Here we focus on increasing bacterial retention in the bladder in order to reduce the number of instillations required and improve antitumor activity. OBJECTIVE: To increase the binding of Ty21a to the bladder wall by surface labeling of the bacteria with adhesion protein FimH and to study its effect in a bladder cancer mouse model. METHODS: Binding of Ty21a with surface-labeled FimH to the bladder wall was analyzed in vitro and in vivo. The antitumor effect of a single instillation of Ty21a+FimH in treatment was determined in a survival experiment. RESULTS: FimH-labeled Ty21a showed significant (p <  0.0001) improved binding to mouse and human cell lines in vitro. Furthermore, FimH labeled bacteria showed ∼5x more binding to the bladder than controls in vivo. Enhanced binding to the bladder via FimH labeling induced a modest improvement in median but not in overall mice survival. CONCLUSIONS: FimH labeling of Ty21a significantly improved binding to bladder tumor cells in vitro and the bladder wall in vivo. The improved binding leads to a modest increase in median survival in a single bladder cancer mouse study.

Precise Morphologic Documentation with Large-format Histology of Clinical Findings in a Bladder Cancer Patient

2013 ◽  
Vol 64 (3) ◽  
pp. 519-521 ◽  
Author(s):  
Andrea B. Galosi ◽  
Liang Cheng ◽  
Antonio Lopez-Beltran ◽  
Francesco Montorsi ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patient ◽  
Clinical Findings ◽  
Bladder Cancer Patient ◽  
Large Format

scholarly journals A model to predict the outcome of the bilharzial bladder cancer patient after radical cystectomy

1987 ◽  
Vol 56 (6) ◽  
pp. 830-833 ◽  
Author(s):  
M Rafla ◽  
AS Ibrahim ◽  
M Sherif ◽  
AJ Valleron
Keyword(s):  
Bladder Cancer ◽  
Cancer Patient ◽  
Radical Cystectomy ◽  
Bladder Cancer Patient
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