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

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)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Mohammad Haroon Asif Choudry其他文献

Mohammad Haroon Asif Choudry的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了