Nfkbia deletion in glioblastomas

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  • 1. NFKBIA Deletion in Glioblastomas
    Denise M. Scholtens
    Paula Andrea Velsquez Viveros
    MedicineUPB 2011

2. INTRODUCTION
3. INTRODUCTION
GLIOBLASTOMA
Tumors are named for the cell types from which they originate.
Glioblastomais the general name for a tumor that arises from the glial tissue, which supports and nourishes the brain.
4. INTRODUCTION
GLIOBLASTOMA
There are several different kinds of glial cells: astrocytes, oligodendrocytes and ependymal cells.
Oligodendrocytes
Astrocytes
Ependymal cells
5. INTRODUCTION
GLIOBLASTOMA MULTIPLE
Is a malignant astrocytoma that contains areas of dead tumor cells.
Gliosarcoma and giantcellglioblastoma are variants of glioblastoma multiforme. Approximately 50% of astrocytomas are glioblastomas.
6. INTRODUCTION
GLIOBLASTOMA MULTIPLE
Glioblastomas contain more than one cell type.
While one cell type may die off in response to a particular treatment, the other cell types may continue to multiply.
It makes very difficult the treatment.
7. INTRODUCTION
EPIDERMAL GROWTH FACTOR
Is a small mitogenic protein that is thought to be involved in mechanisms such as normal cell growth, oncogenesis, and wound healing.
Its over produced in tumors.
EGFR pathway activesNFKB.
8. INTRODUCTION
9. RELATION
When it is inactive, NF-KB is located in the cytoplasm.
Whereas, it is active is transported to the nucleus, where it gets in contact with EGFR and increased its action.
In tumor cells, the NFKB can induce cellular proliferation
10. RELATION
The increased signal in the tumor's cells sent by the EGFR actives the NF-kappa-B receptor, causing the appearance of cancer, in this case, the multiple glioblastoma and the chemotherapy resistance.
11. EGFR
NUCLEUS
NFKBIA
NFKB
WITHOUT NFKB DELETION
12. EGFR
NUCLEUS
NFKB
NFKB DELETION
13. GENERAL OBJECTIVE
14. GENERAL OBJECTIVE:
AnalyzeNFKBIA deletion in glioblastomas
15. MTODOS Y MATERIALES
16. MATERIALES Y MTODOS
17. Tipos de datos:
G= Datos del nmero de copia del gen E= Datos de expresin gnica
C= Datos clnicos M= O6 metilguanina DNA metiltransferasa
S= Secuencia de datos(MGMT)
18. LNEAS CELULARES Y PREPARACIN DEL DNA GENMICO
19. 20. INMUNOBLOT
21. APLICACIN DEL INMUNOBLOT
Se realiz en el estudio para hallar en los pacientes la presencia del gen NFKBIA.
Se sometieron las lneas celulares en SDS, cargado negativamente.
De esa manera, se separaron las protenas segn su tamao y su carga.
22. RESULTADOS
23. RESULTADOS
En la unidad 1, se tomaron 219 glioblastomas, donde el 24,2%poseen delecin a NFKBIA.
se afecta el cromosomas 14, el brazo corto en el loci 13.
24. RESULTADOS
La dosis gnica se asigna, segn la ubicacin del cromosoma.
La supresindeNFKBIAse asociaa una prdida significativadeexpresinenlos 175 glioblastomasen el estudio deunconjuntodonde se haban combinado los datos de genes.
25. RESULTADOS
Se han distinguido en diferentes estudios, varios subtipos de glioblastomas, como son: clsicos, mesenquimales, neuronales y proneuronales. Donde hay delacin en mayor frecuencia en los proneuronales. Las amplificaciones de EGFR son mas comunes en los glioblastomas clsicos. Lo que indica exclusividad para la delecin de NFKBIA y amplificacin de EGFR.
26. RESULTADOS
Se miraron 3 pacientes.
Paciente 1: hay disminucin en la accin de NFKBIA.
Paciente 2: hay un poco de aumento en NFKBIA, sin importar que haya amplificacin de EGFR.
Paciente 3: NFKBIA tiene accin en un 100%, ya que hay presencia de este y EGFR no est amplificndose.
27. DISCUSSION
28. DISCUSSION
29. CONCLUSSION
30. CONCLUSSION
NFKBIA deletionallowsthat NFKB goestonucleus, and it can increase EGFR action, enhacingcellproliferation
Analyzingthefour molecular subtypes of glioblastoma, theresearchfoundthat NFKBIA deletion and EGFR amplificationhaveanspecial exclusive foronlyonesubtype.
31. CONCLUSSION
The researches of the NFKBIA gene, whose absence causes biological situations similar to the increase of EGFR, contributes to the development of possible solutions to glioblastomas and its Resistance to treatment with temozolamide.
In future researches, It will be taken into account not only the alteration of NFKBIA as an inductor of brain neoplasicprocesses. It will be taken into account too the fact that the gene alteration can be found in some variety of tumors such as Hodking lymphoma, Multiple myeloma, melanoma or breast, lung and colon cancer, seeking for efective treatments with bortezomib
32. MAPA CONCEPTUAL
33. 34. GRACIAS