Genetic fingerprint of aggressive colon tumours

1.organoides_tumorales_de_pacientes

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.

Source:

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!

Enriched Tregs for a multitude of research applications

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…]

Which Antibodies for Epigenetics?

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…]

Unraveling the protective role of the stroma

Research performed by David García-Molleví and his team at ICO (Barcelona, Spain), in cooperation with tebu-11018152_928445027176257_6580852836315207360_nbio 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!

PGE2 role in carcinoma chemoresistance via CSC repopulation

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)

[Read more…]

Where to buy Topo inhibitors and analogs?

DNA topoisomerase I and DNA topoisomerase II (Topo I and Topo II) are nuclear enzymes which regulate the topological state of the DNA helix by transiently breaking and rejoining DNA strands. They also play a critical role in fixing DNA damage resulting from an exposure to harmful chemicals or UV rays. Topo small molecule inhibitors are well-known anticancer approaches. Today, they are coming back to the Drug discovery scene just enough to edit a post on Topo inhibitors, from their history and to their availability for in vitro R&D purposes.

[Read more…]

EndoG and ATM cell cycle checkpoint in Leukemogenesis

In a recent publication, Gole B. and Baumann C. demonstrate the role of the apoptotic nuclease EndoG in Mixed-Lineage Leukemia breakpoint cluster region (MLLbcr) destabilisation leading to MLL gene rearrangements and leukemogenesis. (1)

In this study, various engineered stable knockdown cell lines were used as in vitro cellular models.  Two of them are developed by tebu-bio: SilenciX® HeLa/shATM and HeLa/shATR. They have been selected as stable ATM and ATR KD cellular models to investigate the role of ATM (Ataxia Telangiectasia, Mutated) and ATR (ATM and Rad3-related) cell cycle checkpoint pathways in these MLL rearrangements.

The authors also describe a possible cytotoxic-induced model involving EndoG and ATM / RFN20 / H2B cascade in MLLbcr breakage.

About SilenciX stable KD HeLa cells

SilenciX are gene-specific knock-down (KD) engineered HeLa cell lines. The silencing technology used is not integrative, reducing thus potential off-target effects. These KD cellular models are ideal for a broad range of  signal transduction and drug discovery studies (Loss-of-function model, Synthetic lethality…). To date, 100+ HeLa SilenciX cell lines have been designed (customization on other cell types being possible). Recently, BRCA1-KD, BRCA2-KD and p53-KD SilenciX HeLa cells were used to show that  PARP inhibitors are less synthetically lethal in hypoxic conditions. (2)

SilenciX® is a registered trademark of tebu-bio; technology licensed from the Atomic Energy and Alternative Energies Commission (CEA). (3)CEA logo

SilenciX publications

(1) Gole B., Baumann C. et al. “Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress” (2014) Oncogene, pp-1-11. DOI:10.1038/onc.2014.268.

(2) Mennesson E. et al.SilenciX®, novel stable knock-down cellular models to screen new molecular targets through the synthetic lethality approach”  (2014) (“Experimental and Molecular Therapeutics” poster session – AACR 2014, San Diego – Abstract n° 3733.

(3) Further SilenciX publications and information can be found here.

Typical silencing results with HeLa and custom cell lines

Custom SilenciX MCR5 and MCF7 cell lines by tebu-bio

XPA-KD, KIN17-KD and XPC-KD Custom SilenciX MCR5 and MCF7 cell lines by tebu-bio.

HeLa stable KD cell lines by tebu-bio

Stable silencing of tebu-bio SilenciX HeLa stable KD cell lines (DNAPKcs-KD, KIN17-KD, XPA-KD, XPC-KD, ERCC1-KD and XPF-KD).

I hope these data will bring you new opportunities for your research programs. Share this post or leave any comments concerning the tools you are using to perform efficient and robust gene KD below!

 

German Cancer Research Center looking for a Post-doc in Epigenetics

The German Cancer Research Center (DKFZ) is announcing a call for candidates, for a post-doctoral position within the German Consortium for Translational Cancer Research (DKTK) on “Epigenetics and Oncology”:

Other post-doctoral scientist job opportunities open at the DKFZ are…

Return of SIRT1 deacetylase – Why is SIRT1 so attractive in Drug discovery and Stem cell research?

SIRT1 is a NAD dependent class III Histone Deacetylase (HDAC). The tumor suppressor p53 is not the unique SIRT1 substrate. SIRT1 also deacetylates various key protein targets (PTEN, FOX, HIF-1, XPA, SMAD7 …) involved in the regulation of cellular survival, proliferation and angiogenesis.

SIRT1 – an attractive druggable target in oncologyPrimary cells, active enzymes and small molecules for stem cell and Drug discovery research

SIRT1 has rapidly been considered a valuable druggable target because of its implication in p53-dependent apoptosis in response to cellular stress and DNA damage. This enthusiasm was even more enhanced in 2011 when certain studies suggested that a natural dietary polyphenolic compound (Resveratrol) could promote healthy ageing and increase mouse and yeast life span through activation of sirtuins. (1)
Today, SIRT1 returns to the front of the stage with its possible involvement in cellular reprogramming and pluripotency.

[Read more…]

Your copy of the latest Cancer Signaling poster

The latest update of the GeneTex Cancer signaling poster is available. I am pleased to share it with you.

Download it for you and your lab right here !

This poster summarizes the cell signaling events related to gene expression regulation, cell cycle and proliferation and the various regulatory loops between oncoproteins and tumor suppressors seen in cancer but also in neo-angiogenesis and metastasis (inflammation, Cytoskeletal changes and cell migration, autophagy…).

This poster is undoubtedly an ideal educational document for those willing to acquire an overview of the main signaling pathways involved in cancer.