Melanoma treatment lesson

Main Category: Melanoma / Skin Cancer
Article Date: 05 Jan 2005 - 12:00 PDT


For some years ago now biochemotherapy has replaced chemotherapy for the treatment of melanomas. In biochemotherapy, together with chemotherapuetic agents, substances that activate the patient's immune system are used with the objective of obtaining a reinforced immune system in order to help the patient overcome the illness.

Now, however, the activity of a number of these activating substances has been questioned, given that they have not been found to extend the life of the patient compared to that undergoing the habitual chemotherapy treatment. This is why these activating substances and biochemotherapy treatment itself are being questioned and a number of studies suggest the removal of such substances from medication.

Beneficial or prejudicial?

In the Public University of the Basque Country, in 1992, they discovered that one of these activating substances had a prejudicial effect. We are referring to interleukin-2 (IL-2). This activating substance activates the immune system, but also the proliferation of tumorous cells. Thus, metastasis extends even further and the patient does not benefit at all.

Though armed with this fact, the researchers at the Basque University did not discard the possibility that this substance, if used appropriately, could turn out to be beneficial, i.e. its activity had to be better modulated.

The research began with the aim of discovering the processes that activate IL-2 within the cells. Concretely, IL-2 augments the level of glutathionation (GSH) within the cells, glutathione, in turn, being an element that accelerates cellular proliferation. But this GSH compound is found in all cells and, therefore, in cancerous cells. And this is why the metastasis regenerates.

Thus, in order to obtain beneficial effects using IL-2, the glutation in tumorous cells would have to be reduced in an alternative manner, and this was achieved by means of oxothiazolidine-carboxilate (OTZ).

Finding the appropriate pattern of dosage

The OTZ compound had an important function; it had to reduce the glutation level in tumorous cells while leaving the healthy cells alone. In order to achieve this target it was essential to find the most suitable dosage for the administering of all the components, given that the obtained effect greatly depended on the order in which each of the substances was administered.

After a number of years of investigation, researchers have discovered this pattern. Firstly, the OTZ has to be given, then the chemotherapeutic agent and, finally, the IL-2 is administered. They are not single doses and the treatment is much more complex, but the order has to be this one.

Following this dosage pattern, researchers managed to reduce one of the most serious problems in chemotherapy - toxicity. This meant that the chemotherapy dosage could be increased and, if the investigation turned out to be successful, that the life of the patient would be extended. The quality of life would also be enhanced with this new treatment.

This has been demonstrated through trials over many years, starting with mice and, currently, in vitro trials are being undertaken with human cells. Positive results have been achieved in all these trials, the conclusion being that a substance should not be rejected out of hand as it may well be usage of the substance and not the substance itself which is not suitable.

Notes

Researchers:
Ana Alonso Varona (gcpalvaa@lg.ehu.es) and Teodoro Palomares (ocppacat@lg.ehu.es)

Internet reference
http://www.ehu.es

Contact: Garazi Andonegi
garazi@elhuyar.com
Elhuyar Fundazioa

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