Impact of donor-to-recipient weight ratio on survival after bilateral lung transplantation.

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.

Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development.

Clinical studies have defined the core 'genetic blueprint' of a cancer cell, but this information does not necessarily predict the cancer phenotype. Signalling hubs that mediate such phenotype have been identified largely using OMICS platforms that measure dynamic molecular changes within the cancer cell landscape. The pro-oncogenic protein anterior gradient 2 (AGR2) is a case in point; AGR2 has been shown using a range of expression platforms to be involved in asthma, inflammatory bowel disease, cell transformation, cancer drug resistance and metastatic growth. AGR2 protein is also highly overexpressed in a diverse range of human cancers and can be secreted and detected in extracellular fluids, thus representing a compelling pro-oncogenic signalling intermediate in human cancer. AGR2 belongs to the protein disulphide isomerase family with all the key features of an endoplasmic reticulum-resident protein-this gives clues into how it might function as an oncoprotein through the regulation of protein folding, maturation and secretion that can drive metastatic cell growth. In this review, we will describe the known aspects of AGR2 molecular biology, including gene structure and regulation, emerging protein interaction networks and how its subcellular localization mediates its biological functions. We will finally review the cases of AGR2 expression in human cancers, the pathophysiological consequences of AGR2 overexpression, its potential role as a tumour biomarker that predicts the response to therapy and how the AGR2 pathway might form the basis for drug discovery programmes aimed at targeting protein folding/maturation pathways that mediate secretion and metastasis.

Influence of gender donor-recipient combinations on survival after human lung transplantation.

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.

Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21(Waf1/Cip1).

Overexpression of Ras(G12V) 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 p21(Waf1/Cip1) rescues from Ras(G12V)-induced senescence in human mammary epithelial cells (HMECs). Moreover, we isolated a total of 28 miRNAs that prevented Ras(G12V)-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 Ras(G12V)-induced senescence by prevention of Ras(G12V)-induced upregulation of p21(Waf1/Cip1). Our results establish an important role for the cell cycle inhibitor p21(Waf1/Cip1) in growth control of HMECs and extend the repertoire of miRNAs that modulate the activity of this tumour suppressor.