Comparing how significantly the pharmacological treatment of genitourinary cancer in a non-curative setting affects endpoints of survival or response

Prevalence of advanced genitourinary cancer is high considering approximately 70,000 patients die annually of prostate, bladder and kidney cancer in the United States. Treatment is non-curative but along with the aim of relieving symptoms and improving quality of life, patients and doctors are driven by the goal of prolonging life. In modern urological practice, with the ever increasing number of novel therapies, clinical benefit to patients has to be measured by evaluating the trial endpoints of response and survival against adverse events. This is especially true as the population with advanced cancer is increasingly older and co-morbid. Currently, we are in a time of exponential drug development, innumerable registered trials and a vast amount of expenditure on pharmacological cancer treatment. In this era of financial uncertainty, it is even more important for clinicians to objectively assess the benefit of these expensive, moderately effective treatments that still have associated adverse sequelae. We aim to highlight the pivotal data available and put into context the survival benefit we can currently achieve with the pharmacological treatment of advanced genitourinary cancer, allowing us to critically judge whether a potentially toxic systemic treatment is worthwhile or whether it is better to defer to best supportive care. The figures presented are from the key publications that form the basis of international guideline recommendations and are the standard that newly developed treatments must emulate.     

A Cross-Cultural Study of Disordered Eating Attitudes Among Filipino and Caucasian Americans

The present study examines the symptom levels of eating disorders among Filipino and Caucasian college students residing in Hawaii. The study also examines what variables are associated with disordered eating. A self-report questionnaire that included measures of anger discomfort, self-dissatisfaction, body dissatisfaction, and symptoms of eating disorders was administered to Filipino and Caucasian college students. As predicted, females reported higher eating disorder symptom scores than males. However, Filipino males reported higher levels of disordered eating, dieting, and body dissatisfaction than Caucasian males. No association was found between disordered eating and anger discomfort among Filipinos. The results support previous findings of females reporting higher disordered eating attitudes than males, however, Filipino males reported higher disordered attitudes than Caucasian males. Anger discomfort was not associated with disordered eating among Filipinos, supporting past studies that suggest anger management may not be an appropriate treatment for disordered eating among some Asian groups.     

Pericytes: A newly recognized player in wound healing

Pericytes have generally been considered in the context of stabilizing vessels, ensuring the blood barriers, and regulating the flow through capillaries. However, new reports suggest that pericytes may function at critical times to either drive healing with minimal scarring or, perversely, contribute to fibrosis and ongoing scar formation. Beneficially, pericytes probably drive much of the vascular involution that occurs during the transition from the regenerative to the resolution phases of healing. Pathologically, pericytes can assume a fibrotic phenotype and promote scarring. This perspective will discuss pericyte involvement in wound repair and the relationship pericytes form with the parenchymal cells of the skin. We will further evaluate the role pericytes may have in disease progression in relation to chronic wounds and fibrosis.     

Identification of protein complexes in detergent-resistant membranes of Plasmodium falciparum schizonts

Merozoite surface proteins of the human malaria parasite Plasmodium falciparum are involved in initial contact with target erythrocytes, a process that begins a cascade of events required for successful invasion of these cells. In order to identify complexes that may play a role in invasion we purified detergent-resistant membranes (DRMs), known to be enriched in merozoite surface proteins, and used blue native-polyacrylamide gel electrophoresis (BN-PAGE) to isolate high molecular weight complexes for identification by mass spectrometry. Sixty-two proteins were detected and these mostly belonged to expected DRM proteins classes including GPI-anchored, multi-membrane spanning and rhoptry proteins. Proteins from seven known complexes were identified including MSP-1/7, the low (RAP1/2 and RAP1/3), and high (RhopH1/H2/H3) molecular weight rhoptry complexes, and the invasion motor complex (GAP45/GAP50/myosinA). Remarkably, a large proportion of identified spectra were derived from only 4 proteins: the GPI-anchored proteins MSP-1 and Pf92, the putative GPI-anchored protein Pf113 and RAP-1, the core component of the two RAP complexes. Each of these proteins predominated in high molecular weight species suggesting their aggregation in much larger complexes than anticipated. To demonstrate that the procedure had isolated novel complexes we focussed on MSP-1, which predominated as a distinct species at approximately 500 kDa by BN-PAGE, approximately twice its expected size. Chemical cross-linking supports the existence of a stable MSP-1 oligomer of approximately 500 kDa, probably comprising a highly stable homodimeric species. Our observations also suggests that oligomerization of MSP-1 is likely to occur outside the C-terminal epidermal growth factor (EGF)-like domains. Confirmation of MSP-1 oligomerization, together with the isolation of a number of known complexes by BN-PAGE, makes it highly likely that novel interactions occur amongst members of this proteome.     

Occupational sensitization to lupin in the workplace: occupational asthma, rhinitis, and work-aggravated asthma

BACKGROUND: Lupin is a legume. Its seed can be ground into flour and incorporated into food as a protein source. Cases of rhinitis, urticaria, and anaphylaxis from ingestion of lupin have been reported as well as asthma. OBJECTIVE: To present a cross-sectional study of workers in a food processing company who were exposed to lupin and developed occupational allergy secondary to inhaling lupin products. METHODS: Subjects were interviewed using a standardized questionnaire, including demographics and current and past symptoms. They underwent skin prick tests (SPTs) to common aeroallergens and lupin products, spirometry, and off-line exhaled nitric oxide measurement. Symptomatic subjects, sensitized to lupin on SPT, underwent methacholine bronchial provocation challenge. Those with bronchial hyperresponsiveness had specific bronchial provocation challenge to lupin. RESULTS: A total of 53/54 subjects completed testing (98%). Overall, 21% (11/53) had positive SPT results to lupin. The lupin-sensitive group had a trend toward atopy (P = .06). Seven of 11 (64%) subjects in this group were symptomatic; all had rhinitis, and 2 had wheeze. Two subjects had positive methacholine challenges, and 1 had a positive specific bronchial provocation challenge to lupin with both an early-phase and a late-phase response. CONCLUSION: Allergy to inhaled lupin occurs in the workplace. A high sensitization rate on SPT was found, which correlated with symptoms. The clinical significance of cross-reactivity between legumes on SPT is unclear. CLINICAL IMPLICATIONS: Sensitization to the legume, lupin, can occur from exposure at work and carries a high prevalence of clinical symptoms, which in some cases leads to occupational rhinitis and asthma.     

Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor

Replacement of wounded skin requires the initially florid cellular response to abate and even regress as the dermal layer returns to a relatively paucicellular state. The signals that direct this "stop and return" process have yet to be deciphered. CXCR3 chemokine receptor and its ligand CXCL11/IP-9/I-TAC are expressed by basal keratinocytes and CXCL10/IP-10 by keratinocytes and endothelial cells during wound healing in mice and humans. In vitro, these ligands limit motility in dermal fibroblasts and endothelial cells. To examine whether this signaling pathway contributes to wound healing in vivo, full-thickness excisional wounds were created on CXCR3 wild-type (+/+) or knockout (-/-) mice. Even at 90 days, long after wound closure, wounds in the CXCR3(-/-) mice remained hypercellular and presented immature matrix components. The CXCR3(-/-) mice also presented poor remodeling and reorganization of collagen, which resulted in a weakened healed dermis. This in vivo model substantiates our in vitro findings that CXCR3 signaling is necessary for inhibition of fibroblast and endothelial cell migration and subsequent redifferentiation of the fibroblasts to a contractile state. These studies establish a pathophysiologic role for CXCR3 and its ligand during wound repair.