Cancers, Vol. 12, Pages 923: Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Cancers, Vol. 12, Pages 923: Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells Cancers doi: 10.3390/cancers12040923 Authors: Xingru Li Pär Larsson Ingrid Ljuslinder Daniel Öhlund Robin Myte Anna Löfgren-Burström Carl Zingmark Agnes Ling Sofia Edin Richard Palmqvist Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors rela...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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This study was designated to explore the role of cancer stem cells (CSCs) during chemically induced mouse colon carcinogenesis (by 1,2- dimethylhydrazine dihydrochloride, DMH) with/or without the treatment with a targeted (anti-COX-2) therapeutic drug, celecoxib. Two experiments were conducted. The first, a short-term, 16-week mouse colon carcinogenesis bioassay, demonstrates the early stages of colon carcinogenesis. The other is a medium-term, 32-week mouse colon cancer experiment that mimics an end point of colon malignancy. Colon tumors were detected in animals after 32 weeks; histopathologically, they varied from benig...
Source: Journal of Environmental Pathology, Toxicology and Oncology - Category: Environmental Health Tags: J Environ Pathol Toxicol Oncol Source Type: research
CONCLUSIONS: We developed a novel model that provides additional and powerful prognostic information beyond conventional clinicopathological factors for CRC survival prediction. It also provides new insight into the molecular mechanisms underlying the transition from normal tissues to CSCs and formation of tumor tissues. PMID: 32453965 [PubMed - as supplied by publisher]
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Abstract Increasing knowledge of colorectal cancer stem cells (CCSCs) and tumor microenvironment improves our understanding of cellular mechanisms involved in the immunity against colorectal cancer (CRC). Tumor associated antigens were evaluated via RNA-seq and bioinformatics analysis, evoking promising targets for tumor immunotherapy. MUC1 has been demonstrated to participate in the maintenance, tumorigenicity, glycosylation and metastasis of CCSCs, which may provide a new priority for CSC vaccination. In the present study, the vaccination with CCSCs with high expression of MUC1 was evaluated in a murine model fo...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
Abstract Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 µM), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosi...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
n Src family kinases (SFKs) are non-receptor kinases that play a critical role in the pathogenesis of colorectal cancer (CRC). The expression and activity of SFKs are upregulated in patients with CRC. Activation of SFKs promotes CRC cell proliferation, metastases to other organs and chemoresistance, as well as the formation of cancer stem cells (CSCs). The enhanced expression level of Src is associated with decreased survival in patients with CRC. Src-mediated regulation of CRC progression involves various membrane receptors, modulators, and suppressors, which regulate Src activation and its downstream targets through ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Contributors : Clara Morral ; Eduard BatlleSeries Type : Expression profiling by arrayOrganism :Ribosomal RNA (rRNA) transcription and protein synthesis are heterogeneously regulated in colorectal tumors and are gradually shut down during cell differentiation. Cancer stem cell hierarchy and tumor growth is defined by a tumor cell population that displays elevated rRNA and protein synthesis.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Source Type: research
Contributors : Clara Morral ; Eduard BatlleSeries Type : Expression profiling by arrayOrganism :Ribosomal RNA (rRNA) transcription and protein synthesis are heterogeneously regulated in colorectal tumors and are gradually shut down during cell differentiation. Cancer stem cell hierarchy and tumor growth is defined by a tumor cell population that displays elevated rRNA and protein synthesis.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Source Type: research
In a brand-new study, Ivy League researchers report that they’ve isolated a compound in human stem cells called PAPD5 that can treat “telomere diseases” and reverse cellular aging.1 Of course, like many in mainstream medicine, the first thought is how to turn this natural enzyme into a patented drug that targets stem cells to restore telomeres. It’s yet another example of Big Pharma’s attempt to profit from your God-given genes. But you don’t need a “telomere drug” to reverse cellular aging… In a moment, I’ll show you two natural ways you can easily protect your ...
Source: Al Sears, MD Natural Remedies - Category: Complementary Medicine Authors: Tags: Anti-Aging Health Source Type: news
Abstract Cancer stem cells (CSCs) are subpopulations of cancer cells with high self-renewal potential that are involved in tumor progression and recurrence. It has been postulated that CSCs and non-stem cancer cells are inter-convertible. However, precise mechanisms for the plasticity and stability of cancer stemness remain elusive. Here, we demonstrate that CD44-positive colorectal CSC fractions contain two types of cancer cells: "CD44-stable" cells, in which CD44 expression is stably sustained, and "CD44-trasnsient" cells, which are rapidly converted to CD44-negative cells. CD44-stable cells ...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function. On Nutraceutical Senolytics https://www.fightaging.org/archives/2020/05/on-nutraceutical-senolytics/ Nutraceuticals are compounds derived from foods, usually plants. In principle one can find useful therapies in the natural world, taking the approach of identifying interesting molecules and refining them to a greater potency than naturally occurs in order to produce a usefully large therape...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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