Molecular mechanisms of metastasis in prostate cancer

Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone

Copper modulates zinc metalloproteinase-dependent ectodomain shedding of key signaling and adhesion proteins and promotes the invasion of prostate cancer epithelial cells

A disintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs) are zinc metalloproteinases (ZMPs) that catalyse the 'ectodomain shedding' of a range of cell surface proteins including signalling and adhesion molecules. These 'sheddases' are associated with the invasion and metastasis of a range of cancers. Increased serum and tumour tissue levels of copper are also observed in several cancers although little is known about how the metal might promote disease progression at the molecular level. In the current study, we investigated whether copper might regulate the ectodomain shedding of two key cell surface proteins implicated in the invasion and metastasis of prostate cancer, the Notch ligand Jagged1 and the adhesion molecule E-cadherin, and whether the metal was able to influence the invasion of the prostate cancer epithelial cell line PC3. Physiological copper concentrations stimulated the ZMP-mediated proteolysis of Jagged1 and E-cadherin in cell culture models whilst other divalent metals had no effect. Copper-mediated Jagged1 proteolysis was also observed following the pre-treatment of cells with cycloheximide and in a cell-free membrane system, indicating a post-translational mechanism of sheddase activation. Finally, the concentrations of copper that stimulated ZMP-mediated protein shedding also enhanced PC3 invasion; an effect which could be negated using a sheddase inhibitor or copper chelators. Collectively, these data implicate copper as an important factor in promoting prostate cancer cell invasion and indicate that the selective post-translational activation of ZMP-mediated protein shedding might play a role in this process.

Social physique anxiety and physical activity in early adolescent girls : the influence of maturation and physical activity motives

This study considered the influence of maturation on social physique anxiety (SPA), the relationship between SPA and current and future physical activity (PA) levels and the influence of motives for physical activity on this relationship in early adolescent girls (n=162; mean age=11.80±0.33 years). Participants completed the Pubertal Development Scale, the modified Social Physique Anxiety Scale and the Motives for Physical Activity Scale at baseline and the Physical Activity Questionnaire for Older Children at baseline and 6 months later. The girls became less active across the 6 months and girls in the early stages of maturation had significantly lower SPA than the girls in the middle and late stages of maturation. SPA was not related to current or future physical activity in the sample as a whole. Cluster analysis identified four groups with different motive profiles and the High Appearance and Fitness group demonstrated a moderate negative relationship between SPA and PA at phase 1, whereas the other groups did not. These findings indicate that SPA may increase with maturation and the relationship between SPA and PA is dependent on reasons for being active. For girls who are motivated to be active primarily by body-related reasons SPA is likely to lead to lower levels of PA

Helping someone with problem drinking: Mental health first aid guidelines - a Delphi expert consensus study

Background Alcohol is a leading risk factor for avoidable disease burden. Research suggests that a drinker's social network can play an integral role in addressing hazardous (i.e., high-risk) or problem drinking. Often however, social networks do not have adequate mental health literacy (i.e., knowledge about mental health problems, like problem drinking, or how to treat them). This is a concern as the response that a drinker receives from their social network can have a substantial impact on their willingness to seek help. This paper describes the development of mental health first aid guidelines that inform community members on how to help someone who may have, or may be developing, a drinking problem (i.e., alcohol abuse or dependence). Methods A systematic review of the research and lay literature was conducted to develop a 285-item survey containing strategies on how to help someone who may have, or may be developing, a drinking problem. Two panels of experts (consumers/carers and clinicians) individually rated survey items, using a Delphi process. Surveys were completed online or via postal mail. Participants were 99 consumers, carers and clinicians with experience or expertise in problem drinking from Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. Items that reached consensus on importance were retained and written into guidelines. Results The overall response rate across all three rounds was 68.7% (67.6% consumers/carers, 69.2% clinicians), with 184 first aid strategies rated as essential or important by ≥80% of panel members. The endorsed guidelines provide guidance on how to: recognize problem drinking; approach someone if there is concern about their drinking; support the person to change their drinking; respond if they are unwilling to change their drinking; facilitate professional help seeking and respond if professional help is refused; and manage an alcohol-related medical emergency. Conclusion The guidelines provide a consensus-based resource for community members seeking to help someone with a drinking problem. Improving community awareness and understanding of how to identify and support someone with a drinking problem may lead to earlier recognition of problem drinking and greater facilitation of professional help seeking

Development of mental health first aid guidelines on how a member of the public can support a person affected by a traumatic event: a Delphi study

BACKGROUND: People who experience traumatic events have an increased risk of developing a range of mental disorders. Appropriate early support from a member of the public, whether a friend, family member, co-worker or volunteer, may help to prevent the onset of a mental disorder or may minimise its severity. However, few people have the knowledge and skills required to assist. Simple guidelines may help members of the public to offer appropriate support when it is needed. METHODS: Guidelines were developed using the Delphi method to reach consensus in a panel of experts. Experts recruited to the panels included 37 professionals writing, planning or working clinically in the trauma area, and 17 consumer or carer advocates who had been affected by traumatic events. As input for the panels to consider, statements about how to assist someone who has experienced a traumatic event were sourced through a systematic search of both professional and lay literature. These statements were used to develop separate questionnaires about possible ways to assist adults and to assist children, and panel members answered either one questionnaire or both, depending on experience and expertise. The guidelines were written using the items most consistently endorsed by the panels across the three Delphi rounds. RESULTS: There were 180 items relating to helping adults, of which 65 were accepted, and 155 items relating to helping children, of which 71 were accepted. These statements were used to develop the two sets of guidelines appended to this paper. CONCLUSIONS: There are a number of actions which may be useful for members of the public when they encounter someone who has experienced a traumatic event, and it is possible that these actions may help prevent the development of some mental health problems in the future. Positive social support, a strong theme in these guidelines, has some evidence for effectiveness in developing mental health problems in people who have experienced traumatic events, but the degree to which it helps has not yet been adequately demonstrated. An evaluation of the effectiveness of these guidelines would be useful in determining their value. These guidelines may be useful to organisations who wish to develop or revise curricula of mental health first aid and trauma intervention training programs and policies. They may also be useful for members of the public who want immediate information about how to assist someone who has experienced a potentially traumatic event