The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ≥5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than CTCs enumeration or gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression.
Aplasia cutis congenita (ACC) is an uncommon congenital malformation. It is characterized by defects of the skin that occur most frequently on the scalp along the midline, but can also be localized on the trunk, face and limbs, usually with a symmetrical distribution. When it is localized in the skull it can extend to the dura mater, leaving only the thin pia mater to protect the brain. The most common complications related to this disorder are infection, hemorrhage, and, in defects localized on the vertex, meningitis and bleeding from the sagittal sinus can occur with dramatic consequences. In those cases some authors suggest the use of local flaps even if this implies a surgical procedure. In this case a 2.540-kg baby was delivered at 40 weeks of gestation be eutocic delivery, and good adaptation to extrauterine life. At birth the baby showed a large cutaneous and osseous defect at the vertex measuring 68 cm2, equal to almost one third of the calvarial surface, and extended to the dura mater through which it was possible to see the sagittal sinus and the brain surface with its vessels. Skull X-rays showed loss of normal radioopacity of the cranial vault with lack of ossification especially at the parietal level. In our patient we therefore decided to use a composite graft of cultured autologous fibroblasts and keratinocytes to provide coverage, avoiding any surgical procedure and patient morbidity. This technique consists first in an autograft of cultured fibroblasts which has proved to promote the production of type IV collagen, fibronectin and laminin whereby creating an ideal bed for the taking of the graft of cultured keratinocytes, to be put in place a week later. The use of a composite graft with both the derma-like and epithelial components has been also suggested to diminish scarring. Two months after the last graft area was completely closed.
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