ORCID Profile
0000-0001-8006-6832
Current Organisation
University of California Santa Barbara
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544354
Abstract: Histology and immunohistochemical analysis of beta-catenin in adenomas from treated Dclk1Cre/+ Apcfl/fl mice.
Publisher: Wiley
Date: 2023
DOI: 10.1002/ECS2.4342
Abstract: Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) ersity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use‐inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant ersity and inclusive research practices and increased and improved data flow, access, and skill‐building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.C.6550616
Abstract: Adenomatous polyposis coli (APC) truncations occur in many colorectal cancers and are often associated with immune infiltration. The aim of this study was to determine whether a combination of Wnt inhibition with anti-inflammatory (sulindac) and/or proapototic (ABT263) drugs can reduce colon adenomas. i Apc /i sup min/+ /sup and doublecortin-like kinase 1 ( i Dclk1 /i ) sup Cre/+ /sup i Apc /i sup fl/fl /sup mice were exposed to dextran sulphate sodium (DSS) in their drinking water to promote the formation of colon adenomas. Mice were then treated with either a Wnt-signaling antagonist pyrvinium pamoate (PP), an anti-inflammatory agent sulindac or proapoptotic compound ABT263 or a combination of PP+ABT263, or PP+sulindac. Colon adenoma frequency, size, and T-cell abundance were measured. DSS treatment resulted in significant increases in colon adenoma number ( i P /i 0.001, i n /i 5) and burden in i Apc /i sup min/+ /sup ( i P /i 0.01, i n /i 5) and i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup ( i P /i 0.02, i n /i 5) mice. There was no effect on adenomas following treatment with PP in combination with ABT263. Adenoma number and burden were reduced with PP+sulindac treatment in i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup mice ( i P /i 0.01, i n /i 17) and in i Apc /i sup min/+ /sup mice ( i P /i 0.001, i n /i 7) treated with sulindac or PP+sulindac with no detectable toxicity. PP treatment of i Apc /i sup min/+ /sup mice increased the frequency of CD3 sup + /sup cells in the adenomas. The combination of Wnt pathway inhibition with sulindac was more effective in i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup mice and provides an opportunity for killing i Apc /i -mutant colon adenoma cells, indicating a strategy for both colorectal cancer prevention and potential new treatments for patients with advanced colorectal cancer. Outcomes from the results of this study may be translatable to the clinic for management of FAP and other patients with a high risk of developing colorectal cancer. Significance: Colorectal cancer is one of the most common cancers worldwide with limited therapeutic options. APC and other Wnt signaling mutations occur in the majority of colorectal cancers but there are currently no Wnt inhibitors in the clinic. The combination of Wnt pathway inhibition with sulindac provides an opportunity for killing i Apc /i -mutant colon adenoma cells and suggests a strategy for colorectal cancer prevention and new treatments for patients with advanced colorectal cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544357.V1
Abstract: Adenoma tumour development in Apcmin/+ and Dclk1Cre/+ Apcfl/fl mice
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.C.6550616.V1
Abstract: Adenomatous polyposis coli (APC) truncations occur in many colorectal cancers and are often associated with immune infiltration. The aim of this study was to determine whether a combination of Wnt inhibition with anti-inflammatory (sulindac) and/or proapototic (ABT263) drugs can reduce colon adenomas. i Apc /i sup min/+ /sup and doublecortin-like kinase 1 ( i Dclk1 /i ) sup Cre/+ /sup i Apc /i sup fl/fl /sup mice were exposed to dextran sulphate sodium (DSS) in their drinking water to promote the formation of colon adenomas. Mice were then treated with either a Wnt-signaling antagonist pyrvinium pamoate (PP), an anti-inflammatory agent sulindac or proapoptotic compound ABT263 or a combination of PP+ABT263, or PP+sulindac. Colon adenoma frequency, size, and T-cell abundance were measured. DSS treatment resulted in significant increases in colon adenoma number ( i P /i 0.001, i n /i 5) and burden in i Apc /i sup min/+ /sup ( i P /i 0.01, i n /i 5) and i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup ( i P /i 0.02, i n /i 5) mice. There was no effect on adenomas following treatment with PP in combination with ABT263. Adenoma number and burden were reduced with PP+sulindac treatment in i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup mice ( i P /i 0.01, i n /i 17) and in i Apc /i sup min/+ /sup mice ( i P /i 0.001, i n /i 7) treated with sulindac or PP+sulindac with no detectable toxicity. PP treatment of i Apc /i sup min/+ /sup mice increased the frequency of CD3 sup + /sup cells in the adenomas. The combination of Wnt pathway inhibition with sulindac was more effective in i Dclk1 /i sup Cre/+ /sup i Apc /i sup fl/fl /sup mice and provides an opportunity for killing i Apc /i -mutant colon adenoma cells, indicating a strategy for both colorectal cancer prevention and potential new treatments for patients with advanced colorectal cancer. Outcomes from the results of this study may be translatable to the clinic for management of FAP and other patients with a high risk of developing colorectal cancer. Significance: Colorectal cancer is one of the most common cancers worldwide with limited therapeutic options. APC and other Wnt signaling mutations occur in the majority of colorectal cancers but there are currently no Wnt inhibitors in the clinic. The combination of Wnt pathway inhibition with sulindac provides an opportunity for killing i Apc /i -mutant colon adenoma cells and suggests a strategy for colorectal cancer prevention and new treatments for patients with advanced colorectal cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544354.V1
Abstract: Histology and immunohistochemical analysis of beta-catenin in adenomas from treated Dclk1Cre/+ Apcfl/fl mice.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544360
Abstract: Xgal and DCLK1 staining of colon crypts from DCLK1-CreERT2 BAC transgenic mice
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544360.V1
Abstract: Xgal and DCLK1 staining of colon crypts from DCLK1-CreERT2 BAC transgenic mice
Publisher: American Association for Cancer Research (AACR)
Date: 02-02-2022
DOI: 10.1158/2767-9764.CRC-21-0105
Abstract: Adenomatous polyposis coli (APC) truncations occur in many colorectal cancers and are often associated with immune infiltration. The aim of this study was to determine whether a combination of Wnt inhibition with anti-inflammatory (sulindac) and/or proapototic (ABT263) drugs can reduce colon adenomas. Apcmin/+ and doublecortin-like kinase 1 (Dclk1)Cre/+ Apcfl/fl mice were exposed to dextran sulphate sodium (DSS) in their drinking water to promote the formation of colon adenomas. Mice were then treated with either a Wnt-signaling antagonist pyrvinium pamoate (PP), an anti-inflammatory agent sulindac or proapoptotic compound ABT263 or a combination of PP+ABT263, or PP+sulindac. Colon adenoma frequency, size, and T-cell abundance were measured. DSS treatment resulted in significant increases in colon adenoma number (P & 0.001, n & 5) and burden in Apcmin/+ (P & 0.01, n & 5) and Dclk1Cre/+ Apcfl/fl (P & 0.02, n & 5) mice. There was no effect on adenomas following treatment with PP in combination with ABT263. Adenoma number and burden were reduced with PP+sulindac treatment in Dclk1Cre/+ Apcfl/fl mice (P & 0.01, n & 17) and in Apcmin/+ mice (P & 0.001, n & 7) treated with sulindac or PP+sulindac with no detectable toxicity. PP treatment of Apcmin/+ mice increased the frequency of CD3+ cells in the adenomas. The combination of Wnt pathway inhibition with sulindac was more effective in Dclk1Cre/+ Apcfl/fl mice and provides an opportunity for killing Apc-mutant colon adenoma cells, indicating a strategy for both colorectal cancer prevention and potential new treatments for patients with advanced colorectal cancer. Outcomes from the results of this study may be translatable to the clinic for management of FAP and other patients with a high risk of developing colorectal cancer. Colorectal cancer is one of the most common cancers worldwide with limited therapeutic options. APC and other Wnt signaling mutations occur in the majority of colorectal cancers but there are currently no Wnt inhibitors in the clinic. The combination of Wnt pathway inhibition with sulindac provides an opportunity for killing Apc-mutant colon adenoma cells and suggests a strategy for colorectal cancer prevention and new treatments for patients with advanced colorectal cancer.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2022
DOI: 10.1007/S00234-022-02975-0
Abstract: Molecular biomarkers are important for classifying intracranial gliomas, prompting research into correlating imaging with genotype (“radiogenomics”). A limitation of the existing radiogenomics literature is the paucity of studies specifically characterizing grade 2–3 gliomas into the three key molecular subtypes. Our study investigated the accuracy of multiple different conventional MRI features for genotype prediction. Grade 2–3 gliomas diagnosed between 2007 and 2013 were identified. Two neuroradiologists independently assessed nine conventional MRI features. Features with better inter-observer agreement (κ ≥ 0.6) proceeded to consensus assessment. MRI features were correlated with genotype, classified as IDH-mutant and 1p/19q-codeleted (IDH mut /1p19q codel ), IDH-mutant and 1p/19q-intact (IDH mut /1p19q int ), or IDH-wildtype (IDH wt ). For IDH wt tumors, additional molecular markers of glioblastoma were noted. One hundred nineteen patients were included. T2-FLAIR mismatch (stratified as 50%, 25–50%, or 25%) was the most predictive feature across genotypes (p 0.001). All 30 tumors with 50% mismatch were IDH mut /1p19q int , and all seven with 25–50% mismatch. Well-defined margins correlated with IDH mut /1p19q int status on univariate analysis (p 0.001), but this related to correlation with T2-FLAIR mismatch there was no longer an association when considering only tumors with 25% mismatch (p = 0.386). Enhancement (p = 0.001), necrosis (p = 0.002), and hemorrhage (p = 0.027) correlated with IDH wt status (especially “molecular glioblastoma”). Calcification correlated with IDH mut /1p19q codel status (p = 0.003). A simple, step-wise algorithm incorporating these features, when present, correctly predicted genotype with a positive predictive value 91.8%. T2-FLAIR mismatch strongly predicts IDH mut /1p19q int even with a lower threshold of ≥ 25% mismatch and outweighs other features. Secondary features include enhancement, necrosis and hemorrhage (predicting IDH wt , especially “molecular glioblastoma”), and calcification (predicting IDH mut /1p19q codel ).
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22544357
Abstract: Adenoma tumour development in Apcmin/+ and Dclk1Cre/+ Apcfl/fl mice
Location: United States of America
Location: United States of America
No related grants have been discovered for Michael Christie.