Dataset Information

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer.

ABSTRACT: Hyperthermic intravesical chemotherapy (HIVEC)-whereby the bladder is heated to ± 43 °C during a chemotherapy instillation-can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42-43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.

SUBMITTER: Van Hattum JW

PROVIDER: S-EPMC9054747 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer.

Van Hattum J W JW Scutigliani E M EM Helderman R F C P A RFCPA Zweije R R Rodermond H M HM Oei A L AL Crezee J J Oddens J R JR De Reijke T M TM Krawczyk P M PM

Scientific reports 20220429 1

Hyperthermic intravesical chemotherapy (HIVEC)-whereby the bladder is heated to ± 43 °C during a chemotherapy instillation-can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in ...[more]

PMID: 35488115

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Project description:BackgroundBladder intracavitary hyperthermic perfusion chemotherapy (HIPEC) is a promising treatment for non-muscular invasive bladder cancer (NMIBC). However, the molecular mechanisms underlying the response to HIPEC remain poorly understood. This study aimed to elucidate the transcriptomic profiles associated with the response to HIPEC in NMIBC patients.MethodsRNA sequencing was performed on bladder tumor samples from NMIBC patients who underwent HIPEC treatment. Differentially expressed genes (DEGs) between responders and non-responders to HIPEC were identified. Gene ontology and pathway analysis were conducted to explore the biological functions and pathways enriched in the DEGs. Additionally, the expression of specific immune-related genes was evaluated for their association with HIPEC response. The diagnostic efficiency of selected genes in predicting relapse before and after HIPEC treatment was assessed in a validation cohort.ResultsWe assessed the expression status of differentially expressed genes (DEGs) between responders and non-responders to HIPEC. Gene ontology and pathway analysis revealed that DEGs were enriched in immune-related pathways, including cytokine-cytokine receptor interaction, chemokine signaling pathway, and antigen processing and presentation. Furthermore, the expression of several immune-related genes, including ZMAP4, UPP2, and GALR1, was significantly associated with the response to HIPEC. Therefore, the immune system's reaction plays a crucial role in the response to HIPEC in patients with NMIBC. At last, a considerable diagnostic efficiency that tissue TMEFF2, KRT222, and GTSF1 in predicting relapse in NMIBC patients after HIPEC treatment, and ZMAP4, UPP2, and GALR1 in predicting relapse in NMIBC patients before HIPEC treatment in the validation cohort.ConclusionTranscriptomic profiling revealed that immune-related pathways and genes play a crucial role in the response to HIPEC in NMIBC patients. These findings suggest that transcriptomic profiling could provide a valuable tool for predicting treatment outcomes and identifying therapeutic targets for NMIBC.

Project description:BackgroundDue to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) versus IC alone after bladder-sparing surgery in HRBC.MethodsA systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.ResultsA total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1-2, 22.3% vs. grade 3-4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).ConclusionPatients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC.Systematic review registrationPROSPERO, identifier CRD42021232679.

Dataset Information

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer.

Publications

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer.

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