Application of Mucolytic Therapy in Patient-Derived Models of Pseudomyxoma Peritonei
粘液溶解疗法在腹膜假粘液瘤患者来源模型中的应用
基本信息
- 批准号:9808331
- 负责人:
- 金额:$ 17.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcysteineAppendiceal NeoplasmsBiological ModelsBromelainsCharacteristicsClinicalColorectal CancerComputer SimulationCytotoxic agentDimensionsDiseaseDoseDrug CombinationsDrug TargetingEnvironmentFunctional disorderGelGoalsGranulocyte-Macrophage Colony-Stimulating FactorHumanIn VitroIncidenceInstitutionInterleukin-3InternationalIntra-abdominalLongevityMalignant NeoplasmsMalignant neoplasm of ovaryMalignant neoplasm of pancreasModelingMolecularMorbidity - disease rateMucin-2 Staining MethodMucinousMucinous NeoplasmMucolyticsMucous body substanceMusNatureNeoplasm MetastasisNon obeseOperative Surgical ProceduresOrganOrganoidsOutcomePathway interactionsPatientsPeritonealPharmaceutical PreparationsPolymersProductionProteinsPseudomyxoma PeritoneiRare DiseasesResearchRoleSafetySevere Combined ImmunodeficiencyStem Cell FactorTherapeuticTherapeutic InterventionTransgenic OrganismsTransplant RecipientsTumor BurdenTumor TissueXenograft procedurebiomedical referral centercancer cellchemotherapyclinically relevantcombinatorialcytotoxiccytotoxicitydiabeticefficacy testingextracellularhumanized mouseimprovedin vivoin vivo Modelintraperitonealneoplastic cellnovelpreclinical efficacypreclinical studytumor growthtumor xenograft
项目摘要
Abstract
Pseudomyxoma peritonei (PMP), an insidious but lethal malignancy, refers to peritoneal metastases from
mucinous appendix neoplasms (MAN). PMP is poorly responsive to systemic chemotherapy and frequently
recurs despite aggressive and morbid locoregional surgical therapy. For low-grade PMP (LG-PMP), nearly all of
the deleterious clinical consequences are related to compressive organ dysfunction from excessive production
and intra-abdominal accumulation of paucicellular mucus (predominantly composed of mucin 2 [MUC2] protein).
Conversely, high-grade PMP (HG-PMP) is more cellular and invasive, and the abundant extracellular mucus
provides a protective environment for cancer cells to thrive. We hypothesize that reducing extracellular mucus
accumulation will minimize compressive organ dysfunction by decreasing the mucinous tumor burden of PMP
(especially LG-PMP) and improve the efficacy of chemotherapeutic or targeted drugs by removing the protective
mucus barrier surrounding neoplastic cells (especially HG-PMP). In this proposal, we will test the efficacy of
combinatorial mucolytic therapy, using bromelain (BR) + N-acetylcysteine (NAC), to dissolve extracellular mucus
in clinically relevant in vitro and in vivo patient-derived models of LG- and HG-MAN/PMP. Successful outcome
of the proposed studies will overcome a major hurdle for treating PMP, which is the mass-effect and
cytoprotective-effect of abundant extracellular mucus. In addition, our proposed research provides a novel
treatment dimension for PMP that may be applied to mucinous colorectal, pancreatic and ovarian cancers. Our
proposal is feasible since we are a major referral center for the management of patients with PMP, the proposed
drug combination effectively dissolves mucus in-silico, and we have developed in vitro and in vivo patient-derived
models of MAN/PMP that are representative of the clinical disease.
摘要
项目成果
期刊论文数量(0)
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Mohammad Haroon Asif Choudry其他文献
Mohammad Haroon Asif Choudry的其他文献
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{{ truncateString('Mohammad Haroon Asif Choudry', 18)}}的其他基金
Application of mucus modulating multipurpose trypsin nanoparticles to overcome the mucus barrier and deliver mitochondria-targeted anticancer drugs in mucinous carcinoma peritonei
应用粘液调节多用途胰蛋白酶纳米颗粒克服粘液屏障并在腹膜粘液癌中递送线粒体靶向抗癌药物
- 批准号:
10510536 - 财政年份:2022
- 资助金额:
$ 17.02万 - 项目类别:
Application of mucus modulating multipurpose trypsin nanoparticles to overcome the mucus barrier and deliver mitochondria-targeted anticancer drugs in mucinous carcinoma peritonei
应用粘液调节多用途胰蛋白酶纳米颗粒克服粘液屏障并在腹膜粘液癌中递送线粒体靶向抗癌药物
- 批准号:
10693942 - 财政年份:2022
- 资助金额:
$ 17.02万 - 项目类别:
Application of mucus modulating multipurpose bromelain nanoparticles to overcome the mucus barrier in appendiceal pseudomyxoma peritonei
应用粘液调节多用途菠萝蛋白酶纳米颗粒克服阑尾腹膜假粘液瘤粘液屏障
- 批准号:
10290386 - 财政年份:2021
- 资助金额:
$ 17.02万 - 项目类别:
Application of mucus modulating multipurpose bromelain nanoparticles to overcome the mucus barrier in appendiceal pseudomyxoma peritonei
应用粘液调节多用途菠萝蛋白酶纳米颗粒克服阑尾腹膜假粘液瘤粘液屏障
- 批准号:
10457440 - 财政年份:2021
- 资助金额:
$ 17.02万 - 项目类别: