A cancer stem cell population in malignant brain tumors takes an essential part in brain tumor initiation, growth, and recurrence. Growth factors, such as epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor, are shown to support the proliferation of neural stem cells and also may play key roles in gliomagenesis. However, the responsible growth factor(s), which controls maintenance of brain tumor stem cells, is not yet uncovered. We have established three cancer stem cell lines from human gliomas. These cells were immunoreactive with the neuronal progenitor markers, nestin and CD133, and established tumors that closely resembled the features of original tumor upon transplantation into mouse brain. Three cell lines retained their self-renewal ability and proliferation only in the presence of epidermal growth factor (>2.5 ng/ml). In sharp contrast, other growth factors, including fibroblast growth factor-2, failed to support maintenance of these cells. The tyrosine kinase inhibitors of epidermal growth factor signaling (AG1478 and gefitinib) suppressed the proliferation and self-renewal of these cells. Gefitinib inhibited phosphorylation of epidermal growth factor receptor as well as Akt kinase and extracellular signal-regulated kinase 1/2. Flow cytometric analysis revealed that epidermal growth factor concentration-dependently increased the population of CD133-positive cells. Gefitinib significantly reduced CD133-positive fractions and also induced their apoptosis. These results indicate that maintenance of human brain tumor stem cells absolutely requires epidermal growth factor and that tyrosine kinase inhibitors of epidermal growth factor signaling potentially inhibit proliferation and induce apoptosis of these cells.
IntroductionAlthough long‐term crude outcomes of laparoscopic ventral rectopexy for external rectal prolapse (ERP) have been documented, repetitive functional and quality of life (QOL) assessments are scarce. This study assessed midterm annual functional results and QOL after laparoscopic ventral rectopexy for ERP.MethodsThis study consisted of 58 patients and was a retrospective analysis of prospectively collected data. The Fecal Incontinence Severity Index, the Constipation Scoring System, and QOL instruments (ie 36‐item Short‐Form Health Survey and Fecal Incontinence Quality of Life scale) were administered before and after operation.ResultsThere was no mortality or major morbidity. After a median follow‐up of 49 months (6‐92 months), recurrence of ERP was noted in one patient (2%). There were no mesh‐related complications. The median Fecal Incontinence Severity Index score was significantly reduced at 3 months (34 [10‐61] vs 12 [0‐50], P < 0.0001) and remained significantly reduced for 5 years. The median Constipation Scoring System score was significantly reduced at 3 months (14 [9‐20] vs 7 [0‐16], P < 0.0001) and remained significantly reduced for 4 years. No patients developed new‐onset constipation. All of the Fecal Incontinence Quality of Life scales significantly improved overtime for 4 years. All of the 36‐item Short‐Form Health Survey scales were significantly improved at 3 and 6 months, but none of the scales significantly improved after 2 years.ConclusionLaparoscopic ventral rectopexy for ERP was associated with low morbidity, low recurrence, and a midterm improvement in function and fecal incontinence‐specific QOL.
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