Tag: tumor

New imaging technique for deeper insights in breast cancer metastasis

New imaging technique for deeper insights in breast cancer metastasis

A collaborative effort between researchers from DESY, the University Medical Center Hamburg-Eppendorf (UKE), Chalmers University in Sweden and the Paul Scherrer Institute in Switzerland has yielded a cutting-edge multimodal imaging approach to investigate breast cancer tissue. With the help of this technique, researchers can simultaneously extract information about the nanostructure of the tumor and quantify the chemical elements present in a millimeter-scale sample in all three dimensions. A unique combination of research possibilities at PETRA III and new analysis methods enables this high level of detail. 

Breast cancer caused 685 000 deaths globally in 2020 according to the WHO. It is not life-threatening in its earliest form. But if the cancer cells are able to spread further in the tissue to nearby lymph nodes or important organs, this metastasis can be fatal. In a recent pilot study published in Nature Scientific Reports, the team applied this revolutionary imaging approach to a breast cancer sample. The results show how key molecules collectively influence the metastatic mechanism. This breakthrough paves the way for an in-depth investigation of breast cancer metastasis, promising novel therapeutic approaches and personalised treatment strategies, which could ultimately improve patients’ lives if recognized early enough.

Traditional experimental models often fall short, relying on 2D cell cultures or animal models that do not faithfully replicate the complex physiological patterns of human tumor environments. The multimodal imaging approach presented in this study represents a significant step forward by providing simultaneous nanoscale morphological and physiological information from real samples, thus giving researchers information about the shape and composition of real cancer tissue.

André Conceição, the first author and beamline scientist at the PETRA III SAXSMAT beamline P62, emphasises, “Although demonstrated for breast cancer, this approach’s versatility extends to other organs and diseases.”

The study opens avenues for further exploration of breast cancer metastasis and pre-metastatic niches (PMNs). Advanced X-ray multimodal tomography can generate complementary 3D maps for different breast cancer molecular subtypes. It holds the potential to contribute to the development of more targeted and effective strategies for diagnosis and treatment.

Read more on DESY website

Image: 3D vector field of the collagen direction and degree of orientation obtained by SAXS-Tensor-Tomography

Using light to switch drugs on and off

Using light to switch drugs on and off

Scientists at the Paul Scherrer Institute PSI have used the Swiss X-ray free-electron laser SwissFEL and the Swiss Light Source SLS to make a film that could give a decisive boost to developing a new type of drug. They made the advance in the field of so-called photopharmacology, a discipline that develops active substances which can be specifically activated or deactivated with the help of light. The study is being published today in the journal Nature Communications.

Photopharmacology is a new field of medicine that is predicted to have a great future. It could help to treat diseases such as cancer even more effectively than before. Photopharmacological drugs are fitted with a molecular photoswitch. The substance is activated by a pulse of light, but only once it has reached the region of the body where it is meant to act. And after it has done its job, it can be switched off again by another pulse of light.

This could limit potential side effects and reduce the development of drug resistance – to antibiotics, for example.

Licht-switchable drugs

To make conventional drugs sensitive to light, a switch is built into them. In their study, the scientists led by the principal authors Maximilian Wranik and Jörg Standfuss used the active molecule combretastatin A-4, which is currently being tested in clinical trials as an anti-cancer drug. It binds to a protein called tubulin, which forms the microtubules that make up the basic structure of the cells in the body, and also drive cell division. Combretastatin A-4, or “CA4” for short, destabilises these microtubules, thereby curbing the uncontrolled division of cancer cells, i.e. it slows down the growth of tumours.

In the modified CA4 molecule, a bridge consisting of two nitrogen atoms is added, which makes it particularly photoactive. In the inactive state, the so-called azo bridge stretches the molecular components to which it is attached to form an elongated chain. The pulse of light bends the bond, bringing the ends of the chain closer together – like a muscle contracting to bend a joint. Crucially, in its elongated form, the molecule does not fit inside the binding pockets of the tubulin – depressions on the surface of the protein where the molecule can dock in order to exert its effect. However, when the molecule is bent, it fits perfectly – like a key in a lock. Molecules like this, which fit into corresponding binding pockets, are also called ligands.

Read more on the PSI website

Image: Jörg Standfuss (left) and Maximilian Wranik in front of the experimental station Alvra of the Swiss X-ray free-electron laser SwissFEL, where the photopharmacological studies were carried out. In the long term, the aim is to develop drugs that can be switched on and off by light.

Credit: Paul Scherrer Institute/Markus Fischer