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Introduction and hypothesis: Pregnancy in women with spinal-cord injury (SCI) poses a clinical challenge. We hypothesized that changes in the management of neurogenic bladder during pregnancy are commonly required and should receive more attention.Methods: Data were collected by retrospective analysis of medical records and via cross-sectional survey of 52 women with SCI, representing 67 pregnancies, at ten Italian neurourological clinics. All participants provided informed consent.Results: Between 1976 and 2013, 39 participants had one child, 11 had two children, and two had three children. Mean age at the time of SCI was 18 years and at the time of first pregnancy was 30 years. Delivery occurred from weeks 32 to 40 in 98% of first and second pregnancies, and 94% of neonates were healthy. Oxybutynin was used by four women during five pregnancies, which resulted in delivery of healthy babies. Intermittent catheterization was used before 54% of first pregnancies and 39% of second pregnancies. Bladder management was altered during 45% of these pregnancies, and the most common changes were increased use or frequency of intermittent catheterization or use of an indwelling catheter. Urinary tract infections occurred in 48% of pregnancies, and an irregular course was reported in 13% of pregnancies mainly related to tetraplegia and urological complications.Conclusions: Pregnancy in women with SCI generally has good outcomes and limited risks but frequently necessitates changes in the management of neurogenic bladder. High levels of awareness and focused monitoring of bladder issues are recommended. [ABSTRACT FROM AUTHOR]

Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6+/+ and EphB6−/− mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells. However, reintroduction of EPHB6 into colon cancer cells significantly reduced the number of lung metastasis after tail-vein injection in immunodeficient mice, while EPHB6 knockdown in EPHB6-expressing cells increased their metastatic spread. Consistently, although EPHB6 protein expression in a series of 130 primary colorectal tumors was not associated with patient survival, EPHB6 expression was significantly lower in lymph node metastases compared to primary tumors. Our results indicate that the loss of EPHB6 contributes to the metastatic process of colorectal cancer. [ABSTRACT FROM AUTHOR]

EPH signaling deregulation has been shown to be important for colorectal carcinogenesis and genome-wide sequencing efforts have identified EPHA3 as one of the most frequently mutated genes in these tumors. However, the role of EPHA3 in colorectal cancer has not been thoroughly investigated. We show here that ectopic expression of wild type EPHA3 in colon cancer cells did not affect their growth, motility/invasion or metastatic potential in vivo. Moreover, overexpression of mutant EPHA3 or deletion of the endogenous mutant EPHA3 in colon cancer cells did not affect their growth or motility. EPHA3 inactivation in mice did not initiate the tumorigenic process in their intestine, and had no effects on tumor size/multiplicity after tumor initiation either genetically or pharmacologically. In addition, immunohistochemical analysis of EPHA3 tumor levels did not reveal associations with survival or clinicopathological features of colorectal cancer patients. In conclusion, we show that EPHA3 does not play a major role in colorectal tumorigenesis. These results significantly contribute to our understanding of the role of EPH signaling during colorectal carcinogenesis, and highlighting the need for detailed functional studies to confirm the relevance of putative cancer driver genes identified in sequencing efforts of the cancer genome. [ABSTRACT FROM AUTHOR]