GSE125404 Patient-derived scaffolds of colorectal cancer metastases as an organotypic 3D model of liver metastatic colonization ​

In conclusion, our 3D culture system with patient-derived tissue-specific decellularized ECM better recapitulates the metastatic microenvironment compared to conventional 2D culture conditions and represents a relevant approach for the study of liver CRC metastasis formation and progression.Transcriptomic analysis was performed comparing the global gene expression profiles of HT29 cells grown on CRLM and HL scaffolds. The transcriptomic profile of each 3D subtype was compared with HT29 cells grown in plastic. Hierarchical clustering analysis revealed that the gene expression signature of recellularized CRLM scaffolds was more comparable to recellularized HL scaffolds, than to HT29 cells grown in 2D. Gene set enrichment analysis (GSEA) of the differently expressed genes (DEG) up-regulated in recellularized CRLM scaffolds compared to HT29 grown in 2D revealed that genes involved in demethylation, deacethylation and metabolic process belong to the most enriched biological pathways in repopulated-CRLM scaffolds. Comparing the DEG between recellularized CRLM scaffolds vs HT29 grown in 2D with a series of a-priori defined gene-set, called Hallmark, we obtained concordant results with the “HYPOXIA” and “EPITHELIAL_MESENCHYMAL_TRANSITION” pathway, enriched in recellularized CRLM, supporting the idea that 3D culture models are the ability to re-create a complex environment in terms of oxygen tension, nutrients, and metabolic gradient, similarly to the in vivo e...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

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Targeted therapy using monoclonal antibodies conjugated to toxins is gaining space in the treatment of cancer. Here, we report the anti-tumor effect of a new antibody drug conjugate (ADC) delivering a HDAC inhibitor to ErbB2+ solid tumors. Trastuzumab was partially reduced with tris [2-carboxyethyl] phosphine (TCEP) and conjugated to ST7464AA1, the active form of the prodrug HDAC inhibitor ST7612AA1, through a maleimide-thiol linker to obtain the Antibody Drug Conjugate (ADC) ST8176AA1. The average drug/antibody ratio (DAR) was 4.5 as measured by hydrophobic interaction chromatography (HIC). Binding of ST8176AA1 to ErbB2 r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract It is an increasing evidence that long non-coding RNAs (lncRNAs) are involved in tumour initiation and progression. Here, we analysed RNA-sequencing data from the Cancer Genome Atlas (TCGA) datasets. Totally, 1176lncRNAs, 245miRNAs and 2081mRNAs were identified to be differentially expressed (DE) in colon cancer tissues compared with normal tissues. CASC21, a novel lncRNA located in 8q24.21 locus, was significantly overexpressed in 30 colon cancer tissues compared with matched normal tissues by qRT-PCR assay. CASC21 tended to higher expression as the increase of the tumour-node-metastasis (TNM) classifica...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Mucinous KRAS mutated colon/appendix cancers demonstrate unique genotypic and phenotypic characteristics that allow for the rational application of MEK ‐PI3K inhibitor therapy. The present study demonstrates that dual MEK‐PI3K inhibitor therapy (trametinib plus pictilisib) reduces mucinous tumor growth in patient‐derived ex vivo and in vivo models of KRAS mutated mucinous colon/appendix cancer. AbstractMolecular ‐targeted therapies have demonstrated disappointing results against most advanced solid cancers. This may largey be attributed to irrational drug use against unselected cancers. We investigated the efficacy...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.Graphical abstract
Source: Life Sciences - Category: Biology Source Type: research
In conclusion, the encapsulation of doxo in UT-II-targeted liposomes potentiated its delivery in UTR-overexpressing cells and could represent a new tool for the targeting of prostate and colon cancer. PMID: 31929800 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
ncha Graña Figueroa The E3 ubiquitin-ligase Hakai binds to several tyrosine-phosphorylated Src substrates, including the hallmark of the epithelial-to-mesenchymal transition E-cadherin, and signals for degradation of its specific targets. Hakai is highly expressed in several human cancers, including colon cancer, and is considered as a drug target for cancer therapy. Here, we report a link between Hakai and the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity. Hsp90 inhibitors specifical...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: Even if a disseminated site>1 cm in diameter before NACT is invisible during IDS, microscopic disease remains present within it. The appropriate surgical margins for IDS with a favorable prognosis could be secured by resecting a lesion of>1 cm before NACT even if it is invisible during IDS. PMID: 31912684 [PubMed - as supplied by publisher]
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
Abstract Consumption of a high-fat diet has been associated with an increased risk of developing colorectal cancer (CRC). However, the effects of the interaction between dietary fat content and the aryl hydrocarbon receptor (AhR) on colorectal carcinogenesis remain unclear. Mainly known for its role in xenobiotic metabolism, AhR has been identified as an important regulator for maintaining intestinal epithelial homeostasis. Although previous research using whole-body AhR knockout mice has revealed an increased incidence of colon and cecal tumors, the unique role of AhR activity in intestinal epithelial cells (IECs...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer. METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively. RESULTS: DNAJC1...
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
Publication date: Available online 28 December 2019Source: Journal of Photochemistry and Photobiology B: BiologyAuthor(s): Zhen Yang, Hongwei Yang, Xinhua Dong, Minglong Pu, Feihong JiAbstractColon carcinoma is a recurring type of cancer that affects the intestine epithelial with a poor survival rate. It was already proven the anticancer property of hesperidin in various cancers but the bioavailability hesperidin is poor, which hinders the hesperidin usage. In this investigation we synthesized hesperidin loaded Zn2+@ SA/PCT nanocomposites and assessed its anticancer potential against colon cancer (HCT116) cells. Hesperidin...
Source: Journal of Photochemistry and Photobiology B: Biology - Category: Speech-Language Pathology Source Type: research
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