MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas.

Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6fl/fl;MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6fl/fl;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes (P=5 × 10-11). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a. These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies.

Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation.

Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels. In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.

Interrelatedness of marital relations and parent-child relations: a meta-analytic review.

It is widely assumed that a linkage, crucial to the understanding of child behavior, exists between marital and parent-child relationship quality. A meta-analysis of 68 studies was conducted to determine whether this linkage exists and, if so, whether the linkage is positive (as suggested by the spill-over hypothesis) or negative (as suggested by the compensatory hypothesis). Results supported the spillover hypothesis; a positive and nonhomogeneous effect size of moderate magnitude was found (d = 0.46). This suggests that research in this area can move beyond the question of whether a positive or negative association exists to identifying moderators of the association. Examination of the impact of 13 potential moderators did not support the existence of any of these variables that could be adequately examined. This suggests that the link between marital and parent-child relations functions as a more stable force than previously thought.

America's angriest home videos: behavioral contingencies observed in home reenactments of marital conflict.

Sequential analysis was used to compare the conflictual marital interactions of physically aggressive (PA, n = 17), verbally aggressive (VA, n = 15), withdrawing (WI, n = 18), and nondistressed, low-conflict (ND, n = 15) couples to describe behavior patterns characteristic of couples who report different marital conflict styles. Videotapes of couples enacting typical conflicts in their own homes were coded with a system designed to capture the affective aspects of communication. PA couples were characterized by the reciprocity of hostile affect and by rigid, highly contingent behavior patterns that were both stronger and longer lasting than those of other conflictual, but nonviolent, couples. In a limited way, ND couples demonstrated some of the same negative behavior patterns as the conflictual couples, but they were able to exit these negative interaction cycles quickly, which underscores the importance of further research into the de-escalation of conflict.

Analysis of the association between marital relationships and health problems: an interactional perspective.

This article reviews the evidence for a relationship between 3 types of marital variables (marital status, marital adjustment, and marital interaction) and health problems (etiology, course/outcome/treatment) as well as the effect that health problems have on marriage. The mechanisms responsible for these associations also are evaluated. The evidence suggest that marital variables affect health status but that the effect is indirect and nonspecific. The major explanatory model, the stress/social support hypothesis, has provided a broad conceptual framework rather than testable hypotheses. The results of the review suggest, however, that sufficient evidence exists for researchers to focus on exploring specific explanations. A hypothetical model is presented that includes interpersonal, intrapersonal, psychological, and physiological variables. This model is intended as a blueprint for exploration as well as a summary of available evidence.