miRNAs: potent biomarkers in cancer research?

journal.pone.0118220.g002

Expression signals of validated miRNAs that differentiated pancreato-biliary cancer from non-malignant abnormalities (A), or from cancers of other types (B).

A recent paper by Kojima, M. et al. has found a signature of miRNAs to identify patients with pancreato-biliary cancers who could benefit from surgical intervention.

Namely, a combination of eight miRNAs (miR-6075, miR-4294, miR-6880-5p, miR-6799-5p, miR-125a-3p, miR-4530, miR-6836-3p, and miR-4476) achieved a sensitivity, specificity, accuracy and AUC of 80.3%, 97.6%, 91.6% and 0.953, respectively.

In contrast, CA19-9 and CEA gave sensitivities of 65.6% and 40.0%, specificities of 92.9% and 88.6%, and accuracies of 82.1% and 71.8%, respectively, in the same test cohort. This diagnostic index identified 18/21 operable pancreatic cancers and 38/48 operable biliary-tract cancers in the entire cohort.

Finding of this eight miRNAs was possible by using Toray’s 3D profiling technology. This finding is especially important, as it is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology.

microRNAs are stably present in peripheral blood, and are therefore a good candidate for finding prognostic or diagnostic biomarkers.

Studying only the miRNAs available in the literature may limit the novelty of the biomarkers found, so for a wide variety of diseases, a profiling is mandatory in order to find really specific circulating biomarkers.

Toray’s technology is available in Europe as fee-for-services via tebu-bio Laboratories (see Press Release). By exploring the full miRnome (composed by 2,000 miRNAs) with Toray’s 3D-Gene® technology, one might identify slight miRNA expression level changes (including low abundance miRNAs) in blood samples, biopsies FFPE specimens…

Interested in miRNA profiling in cancer research? Leave a message below or browse tebu-bio’s 3D-Gene® miRNA profiling platform web page!

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!

3 validated tools for ubiquitination studies

Elongation of ubiquitin chains, regardless of the linkage, can form polyubiquitin fibrils to initiate the Autophagy pathway. A deficiency of the autophagy causes cytotoxic accumulation of ubiquitin-positive aggregates leading thus  to neurodegenerative diseases (1). A new deubiquitinating enzyme, USP36, highly expressed in human breast and lung cancers, was identified to regulate c-Myc oncoprotein stability in nucleolus. (2) Also, Itch, an E3 HECT Ubiquitin ligase, inhibits MAPK p38α activation through ubiquitylation can be exploited therapeutically to prevent chronic skin inflammation (3). A recent publication by Yumimoto K. et al. determined that expression of FBXW7, the F-box Protein of SCF Ubiquitin Ligase, can suppress cancer metastasis in either non-cell-autonomous or cell-autonomous manner. (4)

Ub proteolysis pathway

Ub and F-box proteins proteolysis pathways.

 

Immunohistochemistry staining of formalin-fixed paraffin-embedded human lung using FBXW7 monoclonal antibody (3ug/ml) (Cat. No. 157H00055294-M02).

Immunohistochemistry staining of formalin-fixed paraffin-embedded human lung using FBXW7 monoclonal antibody (3ug/ml) (Cat. No. 157H00055294-M02).

In this work, researchers used the anti FBXW7 monoclonal antibody  to perform immuno-cyto-chemical staining on breast tissues.

Other tools to study ubiquitination include the use of Tandem Ubiquitin Binding Entities (TUBES) for the isolation and detection of polyubiquitylated proteins. TUBES can be used, in combination with Anti Linear Polyubiquitin antibody to investifgate Uquitin linkages on substrates.

References

  1. Morimoto, D., et.al. (2015). Nature communications. DOI: 10.1038/ncomms7116.
  2. Sun, X.-X., et.al. (2015). PNAS. DOI: 10.1073/pnas.1411713112.
  3. Theivanthiran, B., et.al. (2015). Science. DOI: 10.1126/scisignal.2005903.
  4. Yumimoto, K., et.al. (2015) JCI. DOI: 10.172/JCI78782.

If you are studying the role of ubiquitin and ubiquitination in your model, please leave your comment!

Cytokine signature in airway inflammation with arrays

Chronic Mucosal Inflammation is the hallmark of common airway diseases (ex.  Allergic Rhinitis and asthma). Lipoxin B4(LXB4) is an endogenous mucosal protective mediator decreasing such diseases. LXB4 mechanisms of action remain poorly understood.

Cytokine Quantibody Arrays from Raybiotech and tebu-bio laboratories

Cytokine Quantibody Arrays from Raybiotech and tebu-bio laboratories.

In a recent paper in Mucosal Immunology (Karra, L. et al. (2015) 8; DOI:10.1038/mi.2014.116), Allergic Rhinitis  and asthma murine models have been described to better investigate the role of LXB4 in Mucosal Inflammation. The authors conclude that, in the upper airway, LXB4 significantly decreases nasal mucosal leukocytes and degranulation of Mast Cells (MCs) and Eosinophils. They also show that, in the lower airway, LXB4 significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness.

Inhibition of MC degranulation in vivo by LXB4 is more potent than Dexamethasone (a well-known apoptosis inducing glucocorticoid) with unique profiles for cytokine regulation. This latter  is proved by  quantitative analysis of 20 murine cytokines in a single array (Quantibody Cytokine Array).

These findings indicate that LXB4 carries cell type selective and mucosal protective actions and need to be translated to human models. This publication opens the way to consider lipoxins as new therapeutical candidates.

tebu-bio: European RaybioTech's Certified Laboratory service provider

tebu-bio laboratories are the European RaybioTech’s Certified Laboratory service provider.

The Cytokine Arrays are available as ready-to-use assays. They can also be outsourced to Certified Service Laboratory Providers as fee-for-services. In that case, researchers just send their samples and in return receive the experimental data set. To ensure top quality in the data obtained, Raybiotech’s service providers successfully complete training and certification programs to receive the “RayBiotech Certified Array Service Providers” yellow award.

In Europe, tebu-bio laboratories (France) were among the first laboratories in the world to be certified by Raybiotech in 2012. tebu-bio’s services also cover Quansys BioSciences and FullMoon BioSystems technologies for outsourcing protein profiling and quantification.

Sensitive ELISA for Oxytocin quantification

The neuropeptides, Oxytocin and Vasopressin, were isolated and synthesized by Vincent du Vigneaud at Cornell Medical College in 1953, work for which he received the Nobel Prize in Chemistry in 1955. Oxytocin is a neurohypophysial peptide which is produced in the paraventricular nuclei of the hypothalamus and stored in the posterior pituitary. The molecule consists of nine amino acids linked with a disulfide bond and a semi-flexible carboxyamidated tail. Recent studies have defined Oxytocin’s role in various behaviors like social recognition, pair bonding, anxiety, and maternal behaviors (1-4) but also, male reproductive physiology. (5)

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Hello from Marco from Paris who received a tebu-bio Travel Grant

Here are some photos sent by one of our June Travel Grants Winners !

He is just back from the ISANH Antioxidants World Congress 2015 at the Pasteur Institute. Marco Feligioni

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Innovative solutions in cosmetology: Cosmetic 360

The world’s leading perfumery cosmetics network, Cosmetic Valley, announces that its 2015 Cosmetic-360 Meeting will take place in Paris (October 15 – 16th, 2015).tebu-bio belong to the Cosmetic Valley Network.jpg

As a member of this network, tebu-bio will be participating in this trade show which is focussed on open innovations this year.

Recent advances in R&D in vitro cosmetic testings

Several innovative solutions have been designed by tebu-bio laboratories to better understand the mechanisms of action of ingredients, and also to further characterize efficient compounds.

These solutions cover cell-based and functional assays but also gene expression analysis.

Cell culture platform

Starting with cell culture, tebu-bio benefits from a huge bank of primary human cells (including keratinocytes, fibroblasts, adipocytes, sebocytes…) from various sources (donors with a large range of choice ex. gender, age, type, body zones) to develop tailored experimental projects.

Cosmetic-360, Paris 2015As an example, using keratinocytes from young vs. aged donors gives the opportunity to identify biomarkers involved in senescence and by comparison with those present in young donors, determine pathway and efficiency of active compounds. These projects do not need any artificial aging tools like UV irradiation which can generate pathway specific aging process and are not always representative of all natural mechanisms involved. Another approach uses adipocytes issued from normal or high BMI donors, which are helpful tools for testing all slimming mechanisms, including the adipokine pathway.

In combination with oxygen controlled cell culture devices, tebu-bio offers a wide variety of cell culture models including strict physioxic cell conditions for more predictive results and by modifying oxygen concentration they are able to create oxydative stress assays as well as hypoxic stress environment.

Profiling approaches

After cell culture treatment, tebu-bio’s labs offer unique access to a wide variety of biomarker identification tools (from cell culture supernatants for soluble released signaling biomarkers or intracellular biomarkers impacting cell behaviour). Approaches are multiple to allow high versatility such as :

  • Pathway specific gene profiling arrays (oxydative stress, senescence, innate immunity, inflammation, cell metabolism etc…)
  • Protein profiling arrays for qualitative (like multiple Western Blots with up to 1,350 markers per array) or quantitative (like multiple ELISAs with up to 360 markers at once) approaches. Markers available are soluble ones which will impact cell environment or intracellular ones wich will modify internal cell behaviour.
  • miRNA profiling – highly promising biomarkers are either secreted and found in cell culture supernatant or remain intracellular. miRNAs have the capacity to down regulate RNA translation and are thus powerful mediators of cell activity.

Bioassays

To further complete the analysis of active compounds, functional bioassays are ideal and available as ready-to-use kits or as fee-for-services. The most popular ones include:

Come and meet us at Cosmetic 360 – get your free invitation

I will be pleased to meet you at Cosmetic 360 and discuss the recent advances in cosmetology and in R&D. To receive an invitation to Cosmetic 360 free-of-charge offered by tebu-bio, get in contact via the form below. The number of complimentary inviations available is limited, early application is advised.

Hello from Krisztina in Milan, a Research Travel Grant winner!

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Here are some photos sent by one of our April Travel Grants Winners !

She is just back from the 39th Annual Meeting of the European Working Group on Cardiac Cellular Electrophysiology in conjunction with the EHRA Europace-Cardiostim Congress in Milan.

 

 

 

 

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Facebook Summer Quizz from June 29th to July 5th 2015!

tebu-bio may have been around in Life Sciences for over 60 years, but we’re a young-minded company. Every day, we seek to innovate and meet our customer’s needs… YOUR needs! Finding new products, new techniques is great but it’s essential to share them with you. How well do you know our company….? 

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More data with chemiluminescence imaging platform

Quansys Q-View Imager Pro. Source: tebu-bio.

Quansys Q-View Imager Pro. Source: tebu-bio.

Depending on the phase where your biomarker-related research program is, imaging of protein or antibody arrays has different requirements. For R&D purposes (incl. translational and preclinical ones), a standard imager is more than enough. However, for clinical assays at the late stages, a higher resolution may be needed, especially in view of a future file submission.

Known for the development of the Q-plex platform, which is being used by translational and clinical laboratories worldwide (e.g. to detect Pneumococcus), Quansys has released a new imager, designed for higher throughput (96- and 384-well plates) and clinical-grade research. [Read more…]