Abstract 2924: In vivo CRISPR/Cas9 models of microsatellite instable colon cancer reveal recurrent mutations in putative tumor supressor genes

Background:: Several studies have suggested potential aptitude of polylactic-co-glycolic acid (PLGA)-derived nanoparticles (NPs) to improve the antitumor efficacy of anticancer drugs against colon cancer. Further, conjugation of lectins over the surface of the NPs may ameliorate interaction and thus enhance attachment of NPs with receptors. Objective:: The main goal of the study was to prepare and evaluate targeting potential (in vivo) of the optimized NPs against colorectal cancer. Methods:: The 5-fluorouracil (5-FU) loaded and wheat germ agglutinin (WGA)-conjugated PLGA-NPs (WFUNPs) were prepared and then they were evaluated in vivo for targeting aptitude of formulation using gamma scintigraphy after oral delivery. The WGA-conjugated and non-conjugated optimized NPs were compared for any significant results. Further, optimized formulations were also assessed for different parameters such as radiolabeling efficiency, sodium pertechnetate uptake, stability of NPs, and organ distribution study. Results:: Findings suggested prolonged retention of 99mTc-tagged WFUNPs in the colonic region after 24 h study. Eventually, the outcome from conjugated formulation revealed enhanced bioavailability of the drug in blood plasma for up to 24 h. Conclusion:: In conclusion, WGA-conjugation to NPs could improve the performance of the PLGA-NPs in the treatment of colorectal cancer.

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Large volume spark discharge and plasma jet-technology for generating plasma-oxidized saline targeting colon cancer in vitro and in vivo

Journal of Applied Physics ◽

10.1063/5.0033406 ◽

2021 ◽

Vol 129 (5) ◽

pp. 053301

Author(s):

Eric Freund ◽

Lea Miebach ◽

Ramona Clemen ◽

Michael Schmidt ◽

Amanda Heidecke ◽

...

Keyword(s):

Colon Cancer ◽

Large Volume ◽

Plasma Jet ◽

Spark Discharge

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In vivo sentinel lymph node identification using fluorescent tracer imaging in colon cancer: a systematic review and meta-analysis

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2020.103149 ◽

2020 ◽

pp. 103149

Author(s):

T.A. Burghgraef ◽

A.L. Zweep ◽

D.J. Sikkenk ◽

M.H.G.M. van der Pas ◽

P.M. Verheijen ◽

...

Keyword(s):

Systematic Review ◽

Colon Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Meta Analysis ◽

Fluorescent Tracer ◽

Sentinel Lymph Node Identification ◽

Tracer Imaging

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Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis

Scientific Reports ◽

10.1038/s41598-020-80911-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazim Husain ◽

Domenico Coppola ◽

Chung S. Yang ◽

Mokenge P. Malafa

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Metastasis ◽

Annexin V ◽

Cancer Cell Growth ◽

Ki 67 ◽

Sox2 Expression ◽

Tumour Metastasis

AbstractThe activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and β-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.

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Sophocarpine can enhance the inhibiting effect of oxaliplatin on colon cancer liver metastasis—in vitro and in vivo

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-020-02032-8 ◽

2021 ◽

Author(s):

Yu-Shen Yang ◽

Dan Wen ◽

Xue-Feng Zhao

Keyword(s):

Colon Cancer ◽

Liver Metastasis ◽

Inhibiting Effect ◽

Colon Cancer Liver Metastasis

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The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells

Molecules ◽

10.3390/molecules26072045 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2045

Author(s):

Agnieszka Gornowicz ◽

Anna Szymanowska ◽

Mariusz Mojzych ◽

Robert Czarnomysy ◽

Krzysztof Bielawski ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cathepsin B ◽

Beclin 1 ◽

Special Role ◽

The Novel ◽

Colon Cancer Cells ◽

Sulfonamide Derivative

Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.

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Targeting a Lipid Desaturation Enzyme, SCD1, Selectively Eliminates Colon Cancer Stem Cells through the Suppression of Wnt and NOTCH Signaling

Cells ◽

10.3390/cells10010106 ◽

2021 ◽

Vol 10 (1) ◽

pp. 106

Author(s):

Yeongji Yu ◽

Hyejin Kim ◽

SeokGyeong Choi ◽

JinSuh Yu ◽

Joo Yeon Lee ◽

...

Keyword(s):

Colon Cancer ◽

Notch Signaling ◽

Cultured Cells ◽

Pcr Analysis ◽

Marker Genes ◽

Dependent Manner ◽

Lipid Desaturation ◽

Novel Target

The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.

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