Acting and reacting in life science biotechnologies
Stauprimide is known to prime Embryonic Stem Cells (ESC) by targeting the c-Myc-activating transcription factor NME2. Its mechanism of action is linked to the inhibition of the nuclear localization of NME2 leading to the downregulation of the transcription of the c-myc oncogene.
In a recent study, Bouvard C. et al. evidenced that Stauprimide’s mechanism of action could also be used to pharmacologically targetc-myc transcription in cancers. [Read more…]
The role of the interactions between tumor cells and their microenvironment (TME) is now well-established in various stages of cancer development. Cytokines, produced by both the cancer and the immune cells, actively contribute to these critical connections (see the previous posts related to the crosstalk between cancer and immune cells in relation to tumor escape, immunoediting and immunosurveillance).
In a recent review published in BBA, RayBiotech‘s team highlights the “cytokine signatures and dynamics” seen during cancer development. They also demonstrate the necessity of designing relevant multiplex immunoassays for the profiling and the quantification of cytokines in biomarker and anti-cancer drug discovery programs.
Source:
Valerie Sloane Jones, Ren-Yu Huang, Li-Pai Chen, Zhe-Sheng Chen, Liwu Fu, Ruo-Pan Huang “Cytokines in cancer drug resistance: Cues to new therapeutic strategies” (2016) Biochimica et Biophysica Acta, Volume 1865, Issue 2, 255–265. DOI:10.1016/j.bbcan.2016.03.005.
Following our series of posts on tumour immunity, I’d like to mention an article published by researchers from the Ben-Gurion University of the Negev (Israel). The authors investigated the negative correlation between caffeine consumption and incidence of tumours. Or to say it more simply, intake of caffeine favours the immune system fighting tumours. (1) [Read more…]
The anti-cancer property of the Vitamin K3 (Vitk3) was again recently studied by Dr Meng-Er Huang’s team (Curie Institute, CNRS UMR3348, Paris).
By using in vitro pro-oxydative cellular models, Dr Huang and collaborators observed a cancer-selective cytotoxicity of vitk3 in Peroxyredoxin 1 (PRDX1 aka PRX1)-deficient cancer cell lines.
To further investigate the underlying molecular mechanisms, the authors used a stably PRX1-depleted HeLa cell line (PRX1-) (vs. Control (PRX1+)) under various experimental conditions. They notably treated PRX1- and PRX1+ cell lines by vitk3 and 6 other known anticancer molecules targeting different cellular events (microtubule (vinblastine & taxol); DNA (doxorubicin & daunorubicin); DNA transcription (actinomycin D) and cell cycle (5-FU)). [Read more…]
A publication earlier this year by Bárcena et al. shows that angiogenin plays a crucial role in the onset and development of liver cancer (hepatocellular carcinoma or HCC).
Angiogenin was the first isolated tumor-derived protein with in vivo angiogenic activity, featuring a ribonuclease activity that stimulates ribosomal RNA (rRNA) transcription and cell proliferation. Increased angiogenin serum levels have been associated with the incidence and severity of several human tumors, including HCC. [Read more…]
Patient-derived tumour organoids (mini colon tumours). In blue: cellular nuclei; in red: cellular membranes (Image: Alexandre Calon, IRB Barcelona).
Researchers at the IRB in Barcelona have found a signature of 4-6 genes able to predict the aggressivity of colon tumours, by analysing the tissue surrounding the tumour cells.
The scientists are currently developing a test that enables the identification of patients at risk of relapse after surgical removal of the tumour by measuring these found genes. They also propose to test in patients a particular drug that blocks the metastatic capacity of colorectal cancers in mice. This drug has been already tested using organoids derived from patients’ samples.
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On a more funny note, have a look at the video done this last summer by researchers at the IRB Barcelona!
Any exciting research (or videos!) done over at your laboratory or institute?
We would like to know!
When it comes to the body’s natural defenses, is it possible to have “too much of a good thing”? Absolutely. To spare the host, the immune system needs to distinguish it from the real enemy –infectious agents. Autoimmune disorders occur when this recognition frays and the body’s own cells and tissues are damaged.
That’s where regulatory T cells, or Tregs, come in. [Read more…]
The nucleosome core particle is the fundamental structural unit of the eukaryotic genome. It consists of a histone octamer composed of two H2A-H2B dimers and a H3-H4 tetramer wrapped by ~146 base pairs of DNA. A linker histone (i.e., H1) associates with the nucleosomal dyad as well as with linker DNA on either side of the nucleosome, resulting in the formation of the chromatosome. All the core and linker histones are posttranslationally decorated, with at least 160 total modifications described to date including acetylation, methylation, phosphorylation, propionylation, citrullination, formylation, proline isomerization, butyrylation, ADP ribosylation, ubiquitylation, sumoylation, and the more recently identified glycosylation and crotonylation.
These modifications are thought to impact chromatin functions by either altering chromatin packaging or through the recruitment/inhibition of specific chromatin binding factors. Thus, the combined signal from a particular collection of histone marks constitutes a “histone code” that affects gene expression or other chromatin-based functions. [Read more…]
Research performed by David García-Molleví and his team at ICO (Barcelona, Spain), in cooperation with tebu-
bio laboratories, is being presented at the AACR congress in Philadelphia these days.
The poster describes how cytokine profiling of drug-disrupted tumour cell / fibroblast crosstalk provides insights to understand the protective role of the stroma. Briefly, an array including 174 cytokines was performed on tumour cell / fibroblast co-cultures. Results determine that IL1b and TGFb1 secreted by tumor cells trigger the activation of normal colonic fibroblasts (NCF) to become CAFs. The role of IL1b is not as well known as TGFb1 in a cancer context.
Cytokine arrays were used in order to determine:
i) cytokine profiling of IL1b-treated NCF
ii) profiling of tumor cell-NCF cocultures in the presence of inhibitors of IL1b and TGFb1 signaling, main triggers of NCFactivation.
This poster shows how cytokine profiling can be useful as a complementary approach for microenvironment studies in assessing reciprocal activation of tumour cells and stroma, mediators of such interplay, treatment effectiveness and new target interventions.
Would you like to have a copy of this poster? Contact us!
The involvement of Prostaglandin E2 (PGE2) in cancer development has already been described (see the post “Tumour microenvironment – the dark side of PGE2). Recently, Kurtova et al. confirmed this idea by describing the role of COXII/PGE2 signalling pathway during bladder cancer cytotoxic chemoresistance. (1)