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Abstract: Background: In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. However, some data have suggested a possible effect of gender combinations on survival following lung transplantation. Methods: A total of 249 adult lung transplant recipients at a single center between February 1988 and December 2008, were analyzed retrospectively for donor-recipient gender matching. We compared the mortality by calculating one-term survival rates after transplantation using the Kaplan-Meier method with comparisons using the log-rank (Mantel-Cox) test. Statistical significance of the mean effects of size matching was assessed by paired Student t tests and Wilcoxon signed rank tests. Results: Kaplan-Meier survival analysis shown that male compared to female recipients did not have an effect on outcomes after lung transplantation at 5 years (P = .5379), 10 years (P = .107), 15 years (P = .0841), 20 years (P = .0711). No effect of gender on lung transplantation outcomes was observed with donor-recipient gender mismatches at 5 years (P = .1804), 10 years (P = .1457), 15 years (P = .0731), or 20 years (P = .0629). Similarly, no differences were observed for each gender combination. The degree of size matching was defined as the ratio of donor-to-recipient predicted total lung capacity. The ratios were similar for the donor-recipient gender match and significantly different for the donor-recipient gender mismatch. Conclusions: These analyses suggested that gender was not a significant independent risk factor affecting survival after lung transplantation. Size mismatch caused by gender mismatch did not increase mortality. [Copyright &y& Elsevier]

Overexpression of RasG12V in primary cells induces a permanent growth arrest called oncogene-induced senescence (OIS) that serves as a fail-safe mechanism against malignant transformation. We have performed a genome-wide small interfering RNA (siRNA) screen and a microRNA (miRNA) screen to identify mediators of OIS and show that siRNA-mediated knockdown of p21Waf1/Cip1 rescues from RasG12V-induced senescence in human mammary epithelial cells (HMECs). Moreover, we isolated a total of 28 miRNAs that prevented RasG12V-induced growth arrest, among which all of the miR-106b family members were present. In addition, we obtained a number of hits, miR-130b, miR-302a, miR-302b, miR302c, miR-302d, miR-512-3p and miR-515-3p with seed sequences very similar to miR-106b family members. We show that overexpression of all these miRNAs rescues HMECs from RasG12V-induced senescence by prevention of RasG12V-induced upregulation of p21Waf1/Cip1. Our results establish an important role for the cell cycle inhibitor p21Waf1/Cip1 in growth control of HMECs and extend the repertoire of miRNAs that modulate the activity of this tumour suppressor. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to investigate the relationship between donor-to-recipient weight ratio and post-transplantation survival. Methods: From February 1988 to November 2006, 255 adult bilateral lung transplantation patients from 2 different centers were retrospectively analyzed. The cohort was divided into 4 groups depending on the quartile ranges of the donor-to-recipient weight ratio. A time-to-event analysis was performed for risk of death after transplantation conditional on 5-year survival using Kaplan-Meier and Cox proportional hazards models. Results: The mean weight ratio for the study cohort was 1.23 ± 0.39. For all lung transplant recipients during the study period, survival rate at 5 years was 58%. Median survival was 6.3 years in the cohort subgroup with weight ratio <1.23, whereas the median survival was 7.7 years for the cohort subgroup with weight ratio >1.23. Weight ratio >1.23 recipients had a significant survival advantage out to 5 years compared with weight ratio <1.23 recipients (66.1% vs 51.1%, P = .0126). With the aim to assess underweight and overweight donors vs recipients, we have divided all patients into 4 groups, from quartile 1 to 4, based on donor-to-recipient weight ratio. Weight ratio strata affected overall survival, with quartile 1 (lower weight ratio recipients) experiencing the lowest 5-year survival (39.1%), followed by quartile 2 (57.8%), quartile 4 (68.2%), and quartile 3 (70.3%) recipients. The effect of weight ratio strata on survival was statistically significant for the quartile 1 recipients (lower quartile) as compared with the 3 other quartiles. Conclusions: Our findings show a statistically significant effect of donor-to-recipient weight ratios on bilateral lung transplantation survival. A higher donor-to-recipient weight ratio was associated with improved survival after bilateral lung transplantation and likely reflects a mismatch between a relatively overweight donor vs recipient. In contrast, a lower donor-to-recipient ratio was associated with increased mortality after bilateral lung transplantation. [Copyright &y& Elsevier]

Overexpression of RasG12V in primary cells induces a permanent growth arrest called oncogene-induced senescence (OIS) that serves as a fail-safe mechanism against malignant transformation. We have performed a genome-wide small interfering RNA (siRNA) screen and a microRNA (miRNA) screen to identify mediators of OIS and show that siRNA-mediated knockdown of p21Waf1/Cip1 rescues from RasG12V-induced senescence in human mammary epithelial cells (HMECs). Moreover, we isolated a total of 28 miRNAs that prevented RasG12V-induced growth arrest, among which all of the miR-106b family members were present. In addition, we obtained a number of hits, miR-130b, miR-302a, miR-302b, miR302c, miR-302d, miR-512-3p and miR-515-3p with seed sequences very similar to miR-106b family members. We show that overexpression of all these miRNAs rescues HMECs from RasG12V-induced senescence by prevention of RasG12V-induced upregulation of p21Waf1/Cip1. Our results establish an important role for the cell cycle inhibitor p21Waf1/Cip1 in growth control of HMECs and extend the repertoire of miRNAs that modulate the activity of this tumour suppressor. [ABSTRACT FROM AUTHOR]