RESUMO

BACKGROUND: EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and effect of depleting EGF in moderate-to-severe COPD patients, with an EGF-based vaccine. PATIENTS AND METHODS: A phase I trial was conducted in subjects with moderate or severe COPD. The anti-EGF vaccine schedule consisted of 4 biweekly doses followed by 4 monthly boosters. The primary endpoint was the evaluation of the safety and immunogenicity of the vaccine, together with the change in FEV1 and physical function at week 24. RESULTS: Twenty-six patients with moderate or severe COPD were included in the trial. The vaccine was well tolerated and no serious related adverse events were reported. Ninety percent of the individuals developed a protective antibody response. The specific anti-EGF antibodies had high avidity and were able to inhibit EGFR phosphorylation. At the end of vaccination, serum EGF became undetectable. At week 24, there was a clinically significant improvement in lung function, with a mean change in trough FEV1 of 106 mL. Patients also increased their physical functioning. CONCLUSIONS: The EGF-based vaccine was immunogenic and provoked an EGF exhaustion in patients with moderate-to-severe COPD. Depleting EGF might result in a meaningful increase in FEV1, with good tolerability. The current results provide new avenues to treat chronic inflammatory lung diseases associated with EGFR aberrant signaling.

RESUMO

According to the data from the National Cancer Registry, breast and cervical cancer are the two most common nonskin cancers in Cuban woman. This study was addressed to describe the geographical variation of their incidence at small area level over the period 1999-2003. For each municipality, standardized incidence ratios were calculated and smoothed using a Poisson-Gamma, Poisson-Lognormal and a Conditional Autoregressive (CAR) model. The covariate 'urbanization level' was included in the Poisson-Lognormal and CAR models. The posterior probability of each municipality's relative risk (RR) exceeding unity was computed. Clusters were confirmed using the spatial scan statistic of Kulldorff. The CAR model provided the best fit for the geographical distribution of breast and cervical cancer in Cuba. For breast cancer, a high-risk region was identified in municipalities of Ciudad de La Habana province (CAR-smoothed RR between 1.21 and 1.26). Cervical cancer exhibited two areas with excess risk in the east and extreme west of the island (CAR-smoothed RR range 1.2-2.01 both areas together). Clusters were confirmed only for cervical cancer (P = 0.001 for the most likely cluster and P = 0.003 for a secondary cluster). In conclusion, the study supports the hypothesis of a spatial variation in risk at small area level essentially for cervical cancer and also for breast cancer that probably reflects the territorial distribution of life style and socioeconomic factors. This is the first attempt to introduce this methodology in the framework of the National Cancer Registry of Cuba and we expect to extend its use to forthcoming analyses(AU)

Assuntos

RESUMO

According to the data from the National Cancer Registry, breast and cervical cancer are the two most common nonskin cancers in Cuban woman. This study was addressed to describe the geographical variation of their incidence at small area level over the period 1999-2003. For each municipality, standardized incidence ratios were calculated and smoothed using a Poisson-Gamma, Poisson-Lognormal and a Conditional Autoregressive (CAR) model. The covariate 'urbanization level' was included in the Poisson-Lognormal and CAR models. The posterior probability of each municipality's relative risk (RR) exceeding unity was computed. Clusters were confirmed using the spatial scan statistic of Kulldorff. The CAR model provided the best fit for the geographical distribution of breast and cervical cancer in Cuba. For breast cancer, a high-risk region was identified in municipalities of Ciudad de La Habana province (CAR-smoothed RR between 1.21 and 1.26). Cervical cancer exhibited two areas with excess risk in the east and extreme west of the island (CAR-smoothed RR range 1.2-2.01 both areas together). Clusters were confirmed only for cervical cancer (P = 0.001 for the most likely cluster and P = 0.003 for a secondary cluster). In conclusion, the study supports the hypothesis of a spatial variation in risk at small area level essentially for cervical cancer and also for breast cancer that probably reflects the territorial distribution of life style and socioeconomic factors. This is the first attempt to introduce this methodology in the framework of the National Cancer Registry of Cuba and we expect to extend its use to forthcoming analyses.

Assuntos