Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 µM DXR P<0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P<0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer

Adaptación psicosocial del paciente oncológico ingresado y del familiar cuidador principal

El presente estudio refleja la relación existente entre la adaptación psicosocial del paciente oncológico y su familiar (cuidador principal) en situación de ingreso. La muestra recogida es de 94 personas (pacientes oncológicos y familiares). Se utilizaron un cuestionario sociodemográfico y clínico; la escala de Ansiedad y Depresión Hospitalaria (HAD) para medir ansiedad y depresión; el Cuestionario de Calidad de vida (CCV) que mide satisfacción general y apoyo social y el APGAR familiar para medir el funcionamiento familiar. Los resultados indican que la ansiedad del familiar es significativamente superior a la del paciente. El funcionamiento familiar percibido por el paciente correlaciona negativamente con la depresión del familiar, con la puntuación total de la escala y positivamente con la subescala de satisfacción general del familiar. A mayor edad del paciente se observan puntuaciones mas elevadas en la subescala de depresión y en el total de la escala del HAD. Los familiares con edades comprendidas entre 35 y 55 años obtienen puntuaciones significativamente superiores en depresion. Tanto los pacientes como los familiares casados presentan niveles significativamente superiores de depresión que los solteros. Con todo esto concluimos que la adaptación psicosocial del paciente y del familiar es diferente por ello la intervención psicológica durante el ingreso debería centrarse en atender conjunta e individualmente las necesidades del paciente y el familiar: fomentando las redes de apoyo del familiar, facilitando una mejor comunicación con el paciente, reduciendo la ansiedad del familiar y atendiendo a las necesidades físicas, edad y estado civil del paciente.The present study looks for the relation between the psychosocial distress experienced by the patient and his family caregiver during the period he is hospitalised. The sample is composed by 94 persons (oncology patients and family caregivers). We have used a sociodemographic questionnaire, the Hospital Anxiety and Depression Scale, the "Quality of life Questionnaire" for general satisfaction and social support and the family APGAR for family functioning. The results indicate that the anxiety of the caregiver is significantly higher than the one of the patient. The family functioning perceived by the patient correlates negatively with the depression and positively with the general satisfaction of the family caregiver. We found a correlation between the age and the depression subscale. In the family caregivers group we confirm that the higher scores in depression appear in ages between 35 and 55. Married patients and caregivers obtain higher punctuation in depression compared to unmarried ones. We conclude that the patients psychosocial distress differs from the caregivers distress. The psychological intervention should focus on the individual needs of the patient and the caregiver by promoting the social net of the relatives, supplying a better communication with the patient, reducing the caregivers anxiety and attending the demands derived from physical condition, marital status and ag