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Emodin as a complementary dietary therapy to reduce toxicity of 5 fluorouracil
Phone: (803) 360-1362
Email: angela.murphy@uscmed.sc.edu
Phone: (803) 586-5568
Email: daping.fan@uscmed.sc.edu
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Type: Nonprofit College or University
PROJECT SUMMARYfluorouracilFUhas been the first choice chemotherapy drug for colorectal cancerCRCfor many yearshoweverits clinical utility remains hindered by hematopoietic and gastrointestinal toxicities resulting from its non selectivitySide effects include fatigueloss of appetiteand diarrhea among othersall of which can lead to reduced quality of lifeThe economic burden associated with chemotherapy toxicity is substantiala single hospitalization for prevention of neutropeniaa common side effect of chemotherapycan cost $Given that inflammation has been linked toFU associated toxicitiestargeting inflammation may minimize anticancer agent associated toxicityoptimize cancer treatment dosingand improve clinical outcomesThusidentifying strategies to reduce toxicity ofFU is critical to prevent discontinued or de escalated treatmentEmodina natural anthraquinone derivative found in various Chinese medicinal herbs has been recognized for its ability to target NFB and subsequently reduce inflammationHoweverits effects onFU associated toxicity and adverse physiological effectsi ereduced body weightphysical inactivityfatigabilitypainand muscle weaknesshave not yet been studiedWe have collected convincing preliminary data that supports further investigation of emodin as a complementary agent to use withFU chemotherapy in CRCwe have reported that emodin is an effective anti inflammatory agent that acts directly on NFBwe show that emodin is effective at reducing tumorigenesis including CRCwe show that emodin can abolishFU chemotherapy induced intestinal inflammation and mucositiswe indicate that emodin can offset the aforementioned adverse physiological outcomes that are associated withFU administrationandwe show that the doses of emodin that promotes these beneficial effects do not exhibit any side effectsThe long term goal is to move this fundamentally novel complementary dietary compound towards human clinical trials as an innovative agent for use with chemotherapyIn this Phase I STTR project we will rigorously test the hypothesis that dietary emodin will reduce the toxicity associated withFU chemotherapy and this will result in improved therapeutic outcomeThree specific aims are proposedevaluate the effect of emodin on toxicity and adverse effects associated withFU chemotherapyestablish the effective plasma and colon tissue levels and dosing interval for emodinandperform a subchronic oral toxicity screening of emodin in miceThe success of our proposed phase I STTR study will further the development of emodin as a new complementary strategy for use with chemotherapy in CRCThis safeeffectiveand low cost agent has the potential to reduce the toxicity and increase the efficacy of chemotherapy agentsA follow up Phase II STTR program will expand on these initial studies tocomplete efficacy studies of emodin andFU combination in mouse models of CRC andcomplete advanced pharmaceutical toxicology studies in miceThe overall goal of Phase II will be to position AcePre LLC for an FDA Pre Investigational New Drug package PROJECT NARRATIVEfluorouracil has been the first choice chemotherapy drug for colorectal cancer for many yearshoweverits clinical utility remains hampered by hematopoietic and gastrointestinal toxicities resulting from its nonselectivityThere is evidence to suggest that emodina natural anthraquinone derivative found in various Chinese medicinal herbsmay reduce the toxicity of chemotherapy agentsWe will perform dose escalating studies to establish the dose range by which emodin can reduce the toxicity and adverse physiological effects offluorouracil chemotherapywhich will move this fundamentally novel complementary dietary compound towards human clinical trials as an innovative agent for use with chemotherapy
* Information listed above is at the time of submission. *