logo IDIBELL
Català  |   Castellano  |   English
Search
The InstituteResearchWhat's onPlatformsJoin us
 

News

boto imprimir
Date: 22/02/2016

Identify a biochemical alteration responsible for the resistance of the most aggressive brain tumors


 

Researchers at the Institute of Neurosciences, UAB (INC) have identified the biochemical and molecular alterations leading to resistance to radiotherapy and chemotherapy in glioblastoma, the most aggressive brain tumor. The finding could allow, in the future, to design new, more effective therapies.

 

Glioblastoma is the most aggressive manifestation of brain tumors. Due to the high invasive capacity and infiltrative uncontrolled growth, this tumor is particularly difficult to treat. Currently, the established treatment for patients with these tumors is the combination of surgery (when possible), radiation and chemotherapy. This therapy has proved somewhat effective, increasing the overall survival of patients about 15 months. However, this approach remains ineffective to completely eradicate the malignant cells and, unfortunately, recurrences are one of the characteristic features of this cancer.

 

A team of researchers from the Institute of Neuroscience at the UAB, together with the Bellvitge Biomedical Research Institute, University of Barcelona, the Bellvitge University Hospital and the Catalan Institute of Oncology has identified a common molecular alteration in glioblastoma. Researchers have found that cells from this type of tumor houses a common intrinsic defect consisting of an inability to degrade its genetic material during apoptosis, the most important form of programmed cell death induced by radiotherapy and chemotherapy agents.

 

This defect is related to an enzyme: DFF40 / CAD (Death Fragmentation Factor 40 kDa subunit / caspase-Activated DNase). This enzyme is essential for cell DNA degradation during apoptosis, and appears decreased and incorrectly localized in tumor cells compared to non-tumor. Researchers have observed that overexpression of the enzyme allows glioblastoma cells properly degrade its genomic content, according to what is expected of an apoptotic cell death.

 

DNA degradation during apoptosis is essential for the subsequent removal of cellular debris take place correctly. In fact, lack of degradation and removal of genetic material from malignant cells could have detrimental consequences for the organism, such as regrowth of new tumoral processes, often more aggressive than the original.

 

Despite efforts over the last decade, until now had not found any common genetic or biochemical defect in glioblastoma cells. The discovery of low expression levels of the endonuclease enzyme DFF40 / CAD and the observed deficiency to degrade and properly compacting genetic material, are a potential molecular marker in this tumor. In addition, the fact that this alteration has been observed in all the cases studied suggests its possible relevance for understanding the aggressiveness of this cancer. The researchers hope that these new results will help us better understand what is happening inside the tumor, and perhaps in the future, allow us to design new and more effective therapies for this deadly disease.

 

This finding is the result of close collaboration between basic research and clinical. Dr. Victor J. Yuste, researcher at the Department of Biochemistry and Molecular Biology at the UAB and the Institute of Neuroscience at the UAB, has led a multidisciplinary team of researchers in basic research, Neuro-oncologists, pathologists and neurosurgeons from the Institute of Neurosciences, the Centre in Network for Biomedical Research on Neurodegenerative Diseases (CIBERNED), the Bellvitge Biomedical Research Institute, the University of Barcelona, the Bellvitge University Hospital and the Catalan Institute of Oncology. This research has been supported by Ministerio de Economía y Competitividad, with cofounding with ERDF funds, and it appears published in Neuro-Oncology, the leading journal in the field.

 

 

Original article:

 

An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells. Sánchez-Osuna M, Martínez-Escardó L, Granados-Colomina C, Martínez-Soler F, Pascual-Guiral S, Iglesias-Guimarais V, Velasco R, Plans G, Vidal N, Tortosa A, Barcia C, Bruna J, Yuste VJ. Neuro Oncol. 2016 Jan 10. pii: nov315. [Epub ahead of print]





foto Histological section of a glioblastoma. Blue nuclei shown. In green GFAP protein (which shows astroglial cells and tumor cells) is detected. The DFF40 / CAD endonuclease shown dyed in red (photo Dr. Carlos Barcia)
Histological section of a glioblastoma. Blue nuclei shown. In green GFAP protein (which shows astroglial cells and tumor cells) is detected. The DFF40 / CAD endonuclease shown dyed in red (photo Dr. Carlos Barcia)

Share/Bookmark
 
© 2016 Institut d'Investigació Biomèdica de Bellvitge



Results by pageInitial date
Select date
TitleFinal date
Select date
Search


Your password is about to expire. Please, write in a new password to continue

Remember this password allows you to access to all IDIBELL’s web applications

New password:
Confirm new password:

Accept



Your password is about to expire. Please, write in a new password to continue

Remember this password allows you to access to all IDIBELL’s web applications

New password:
Confirm new password:

Accept


Cancell

Passwords doesn’t match
The password must have at least 6 characters
The new password can not contain special characters
User register

Name
Surname
Second Surname
E-mail
User
Password
Language


Accept


Cancell




Encara no heu contestat l'enquesta de satisfacció sobre la píndola de compres i contractacions. No trigareu més de cinc minuts a fer-ho. La vostra opinió és molt important per millorar l’IDIBELL.

Voleu fer l’enquesta ara?

Yes

No




Further personal and contact information is needed to maintain IDIBELL databases.

Do you wish to fill the form now?

Yes

No





Please, remember to introduce your holiday’s planning in the application

Accept

Cancell