Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors

Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Long-term followup results of 1 cycle of adjuvant bleomycin, etoposide and cisplatin chemotherapy for high risk clinical stage I nonseminomatous germ cell tumors of the testis

PURPOSE: We evaluated the long-term outcome after 1 cycle of adjuvant modified bleomycin, etoposide and cisplatin chemotherapy in patients who underwent orchiectomy for high risk clinical stage I nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: Between 1995 and 1999 a consecutive series of 44 patients underwent orchiectomy for clinical stage I nonseminomatous germ cell tumor of the testis, followed by a single postoperative cycle of adjuvant modified bleomycin, etoposide and cisplatin for vascular or lymphatic tumor invasion, and/or a predominance (50% or greater) of embryonal carcinoma. RESULTS: Four of the 44 patients were excluded from analysis. Of the patients 35 had no evidence of disease at a median followup of 99 months (range 60 to 134). One patient with progression after 13 months showed complete remission after 3 cycles of salvage bleomycin, etoposide and cisplatin chemotherapy but he died of pneumonia 4 weeks after the third course. Two patients underwent orchiectomy for contralateral testis cancer at 18 and 42 months, respectively, followed by an additional 3 cycles of adjuvant chemotherapy. They remained relapse-free for 4 and 92 months, respectively. The former patient was lost to followup after 4 months. Two other patients were disease-free at 10 and 31 months, respectively, and were lost to followup thereafter. Late side effects were tinnitus in 3 patients and involuntary childlessness in 3, of whom 2 had cryptorchidism of the contralateral testis. Nine patients fathered children. CONCLUSIONS: One cycle of bleomycin, etoposide and cisplatin effectively decreases the risk of relapse in patients with high risk stage I nonseminomatous germ cell tumor of the testis. It has minimal side effects and can be a valuable alternative to retroperitoneal lymph node dissection.

"Of course I will...": The combined effect of certainty and level of expectancies on persistence and performance

The importance of performance expectancies for the prediction of regulation of behavior and actual performance has long been established. Building on theories from the field of social cognition, we suggest that the level of performance expectancies, as well as the certainty of the expectancy, have a joint influence on an individual’s beliefs and behavior. In two studies (one cross sectional using a sample of secondary school students and one longitudinal using a sample of university students) we found that expectancies more strongly predicted persistence, and subsequent performance, the more certain the expectancy was. This pattern was found even if prior performance was controlled, as in Study 2. The data give an indication that it may be useful to include certainty as an additional variable in expectancy models.

Should I Stay or Should I Go? Career Choice Intentions of Students with Family Business Background

Personal and motivational patterns of intentional founders have been researched in great depth; however, antecedents to career choices of intentional successors have been conspicuously missing in entrepreneurship research. By drawing on theory of planned behavior, we investigate how intentional founders, successors, and employees differ in terms of locus of control and entrepreneurial self-efficacy as well as independence and innovation motives. We find that transitive likelihood of career intent depends on degree of entrepreneurial self-efficacy and the independence motive. Unexpectedly, we see that high levels of internal locus of control lead to a preference of employment, which challenges traditional entrepreneurship research and suggests that the feasibility of an entrepreneurial career path does not automatically make it desirable. Our findings suggest that students with family business background are pessimistic about being in control in an entrepreneurial career, but optimistic about their efficacy to pursue an entrepreneurial career.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.