ABSTRACT
Present cancer disease models - typically based on cell cultures and animal models that lack the human tumor microenvironment (TME) - are extremely poor predictors of human disease outcomes. Microscale cancer models that combine the micromanipulation of tissues and fluids offer the exciting possibility of miniaturizing the drug testing workflow, enabling inexpensive, more efficient tests of high clinical biomimicry that maximize the use of scarce human tissue and minimize animal testing. Critically, these microscale models allow for precisely addressing the impact of the structural features of the heterogeneous TME to properly target and understand the contributions of these unique zones to therapeutic response. We have recently developed a precision slicing method that yields large numbers of cuboidal micro-tissues ("cuboids", â¼ (400 µm) 3 ) from a single tumor biopsy. Here we evaluate cuboids from syngeneic mouse tumor models and human tumors, which contain native immune cells, as models for drug and immunotherapy evaluation. We characterize relevant TME parameters, such as their cellular architecture (immune cells and vasculature), cytokine secretion, proteomics profiles, and their response to drug panels in multi-well arrays. Despite the cutting procedure and the time spent in culture (up to 7 days), the cuboids display strong functional responses such as cytokine and drug responses. Overall, our results suggest that cuboids make an excellent model for applications that require the TME, such as immunotherapy drug evaluations, including for clinical trials and personalized oncology approaches.
ABSTRACT
Objective: Double-J (DJ) ureteric stents are commonly placed perioperatively for semirigid or flexible ureteroscopic renal surgery. It is believed that lesser stent material within the bladder mitigates stent-related symptoms. This study aimed to evaluate the J-Fil ureteral stent, a single pigtail suture stent compared with conventional DJ stent in relation to stent symptoms in an Asian population undergoing ureterorenal intervention. Methods: Based on internal audit committee recommendation approval, the records of 50 patients retrieved, available data of 41 patients who were prospectively enrolled into two groups (Group 1 [J-Fil stent group], n=21 and Group 2 [DJ stent group], n=20) between August 2020 to January 2021, were analysed. Parameters compared were nature of procedure, stone location and size, ease of deployment or removal, and complications. A modified universal stent symptom questionnaire was used to assess morbidity of stent symptoms within 48 h of insertion and at removal. Results: Both groups had similar median age, distribution in male to female ratio, and stone size. The overall median universal stent symptom questionnaire score at insertion was similar for bladder pain, flank or loin pain, and quality of life between Group 1 and 2; however, at removal Group 1 fared significantly better than Group 2, especially for flank or loin pain and pain at voiding. Both groups had similar ease in insertion with no hospital readmissions. Conclusion: Our audit favoured the single pigtail suture stent in Asian ureters in mitigating stent-related issues. It showed a good safety profile with easy deployment and removal. It promises a new standard in stenting.
