ArticleTranslational research : the journal of laboratory and clinical medicine2021
Improved chemosensitivity following mucolytic therapy in patient-derived models of mucinous appendix cancer.
Article in Translational research : the journal of laboratory and clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Intra-Tumoral Mucolytic Therapy for Unresectable Pseudomyxoma Peritonei: Results of a Single-Center Expanded Access Program.Annals of surgical oncology · 2026Article
- Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.eGastroenterology · 2024Article
- The role of local ablative therapy in patients with advanced invasive mucinous adenocarcinoma of the lung.Journal of cancer research and clinical oncology · 2024Article
- Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.Annals of surgical oncology · 2024Article
- Pulmonary mucinous adenocarcinoma: An overview of pathophysiology and advancements in treatment.Heliyon · 2024Review
- Intraperitoneal BromAcCancers · 2023Article
- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
- Bromelain and acetylcysteine (BromAcAmerican journal of cancer research · 2023Review
- Anticancer properties of bromelain: State-of-the-art and recent trends.Frontiers in oncology · 2022Review
- Organoids From Mucinous Appendiceal Adenocarcinomas as High-Fidelity Models for Individual Therapy.Frontiers in medicine · 2022Article
- A novel method for potentiation of chemotherapy in soft tissue sarcomas with BromAc.American journal of translational research · 2022Article
- The effect of intraperitoneal administration of BromAc on blood parameters: phase 1 study.Discover oncology · 2021Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Abundant intraperitoneal (IP) accumulation of extracellular mucus in patients with appendiceal mucinous carcinoma peritonei (MCP) causes compressive organ dysfunction and prevents delivery of chemotherapeutic drugs to cancer cells. We hypothesized that reducing extracellular mucus would decrease tumor-related symptoms and improve chemotherapeutic effect in patient-derived models of MCP. Mucolysis was achieved using a combination of bromelain (BRO) and N-acetylcysteine (NAC). Ex vivo experiments of mucolysis and chemotherapeutic drug delivery/effect were conducted with MCP and non-MCP tissue explants. In vivo experiments were performed in mouse and rat patient-derived xenograft (PDX) models of early and late (advanced) MCP. MCP tumor explants were less chemosensitive than non-MCP explants. Chronic IP administration of BRO + NAC in a mouse PDX model of early MCP and a rat PDX model of late (advanced) MCP converted solid mucinous tumors into mucinous ascites (mucolysis) that could be drained via a percutaneous catheter (rat model only), significantly reduced solid mucinous tumor growth and improved the efficacy of chemotherapeutic drugs. Combination of BRO + NAC efficiently lyses extracellular mucus in clinically relevant models of MCP. Conversion of solid mucinous tumors into mucinous ascites decreases tumor bulk and allows for minimally invasive drainage of liquified tumors. Lysis of extracellular mucus removes the protective mucinous coating surrounding cancer cells and improves chemotherapeutic drug delivery/efficacy in cancer cells. Our data provide a preclinical rationale for the clinical evaluation of BRO + NAC as a therapeutic strategy for MCP.
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