Untitled - Red Temática de investigación cooperativa en cáncer

P-03
TETRACHLORODIBENZO-P-DIOXIN DISRUPTS INTRACELLULAR
CALCIUM HOMEOSTASIS IN HUMAN NEURONAL CELL LINE SHSY5Y
MORALES-HERNÁNDEZ A 1 , SÁNCHEZ-MARTÍN F J 1 , M P HORTIGÓN VINAGRE M P 1 , HENAO F 1 ,
MERINO JM 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
The tumorigenic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces neurotoxic
effects that alters neurodevelopment and behavior both during development and adulthood.
There are many ongoing efforts to determine the molecular mechanisms of TCDDmediated
neurotoxicity, the signaling pathways involved and its molecular targets in neurons.
In this work, we have used SHSY5Y human neuroblastoma cells to characterize the
TCDD-induced toxicity. TCDD produces a loss of viability (EC50 = 292 ± 28 nM) linked to an
increased caspase-3 activity, PARP-1 fragmentation, DNA laddering and nuclear fragmentation,
in a similar way than staurosporine, a prototypical molecule of apoptosis induction.
In addition, TCDD produces a decrease of mitochondrial membrane potential and an increase
of intracellular calcium concentration. Finally, based on the high lipophilic properties of
the dioxin, we test the TCDD effect on the membrane integrity using sarcoplasmic reticulum
vesicles as a model. TCDD produces calcium efflux through the membrane and an anisotropy
decrease that reflects an increase in membrane fluidity. Altogether these results support
the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells provokes the disruption
of calcium homeostasis, probably affecting membrane structural integrity, leading to an
apoptotic process.
P-04
CHILDHOOD SOLID TUMOURS SURVIVAL IN SPAIN 1980-2006:TIME
TRENDS AND VARIATIONSBY AGE AND SEX
FELIPE-GARCÍA S 1 , SÁNCHEZ DE TOLEDO-CODINA J 2 , ACHA GARCÍA T 3 , SASTRE–URGELLES A 4 ,
NAVAJAS GUTÍERREZ A 5 , PERIS-BONET R 1
1
REGISTRO NACIONAL DE TUMORES INFANTILES. UNIVERSITAT DE VALENCIA (RD06/0020/0033)
2
SERVICIO DE ONCOLOGÍA Y HEMATOLOGÍA PEDIÁTRICA. HOSPITAL UNIVERSITARIO VALL D’HEBRON,
BARCELONA (RD06/0020/1021)
3
UNIDAD DE ONCOLOGÍA PEDIÁTRICA. HOSPITAL MATERNO INFANTIL CARLOS HAYA, MÁLAGA
4
SERVICIO DE ONCOLOGÍA INFANTIL. HOSPITAL LA PAZ, MADRID
5
UNIDAD DE ONCOLOGÍA INFANTIL. HOSPITAL DE CRUCES. BARACALDO, BIZCAIA
Objectives: To document time trends and variations by age and sex of 5-year survival in
childhood solid tumours in Spain.
Material and methods: Retrospective hospital-based (paediatric oncology units) cohort
study. Subjects were 9383 children, aged 0-14 years, diagnosed in 1980-2006 with an incident
solid tumour (Groups III to XII of the International Classification of Childhood Cancer).
Periods 1980-2006 and 1990-2006 were analyzed for trends; and 1995-2004 for comparisons
by sex and age. Observed survival was estimated by Kaplan-Meier method for cohorts
defined by year of incidence. 5-year follow-up after diagnosis was active. Differences by sex
and age, and trends were tested with the log-rank and the log-rank for trend respectively.
Results: Overall survival of solid tumours increased significantly (p