ROBO1, a tumor suppressor and critical molecular barrier for localized tumor cells to acquire invasive phenotype: Study in African‐American and Caucasian prostate cancer models

High‐risk populations exhibit early transformation of localized prostate cancer (CaP) disease to metastasis which results in the mortality of such patients. The paucity of knowledge about the molecular mechanism involved in acquiring of metastatic behavior by primary tumor cells and non‐availability of reliable phenotype‐discriminating biomarkers are stumbling blocks in the management of CaP disease. Here, we determine the role and translational relevance of ROBO1 (an organogenesis‐associated gene) in human CaP. Employing CaP‐progression models and prostatic tissues of Caucasian and African‐American patients, we show that ROBO1 expression is localized to cell‐membrane and significantly lost in primary and metastatic tumors. While Caucasians exhibited similar ROBO1 levels in primary and metastatic phenotype, a significant difference was observed between tumor phenotypes in African‐Americans. Epigenetic assays identified promoter methylation of ROBO1 specific to African‐American metastatic CaP cells. Using African‐American CaP models for further studies, we show that ROBO1 negatively regulates motility and invasiveness of primary CaP cells, and its loss causes these cells to acquire invasive trait. To understand the underlying mechanism, we employed ROBO1‐expressing/ROBO1‐C2C3‐mutant constructs, immunoprecipitation, confocal‐microscopy and luciferase‐reporter techniques. We show that ROBO1 through its interaction with DOCK1 (at SH3‐SH2‐domain) controls the Rac‐activation. However, loss of ROBO1 results in Rac1‐activation which in turn causes E‐Cadherin/β‐catenin cytoskeleton destabilization and induction of cell migration. We suggest that ROBO1 is a predictive biomarker that has potential to discriminate among CaP types, and could be exploited as a molecular target to inhibit the progression of disease as well as treat metastasis in high‐risk populations such as African‐Americans.     

‘We are survivors too’: African‐American youths' experiences of coping with parental breast cancer

Objective: To explore how African‐American youth cope with the diagnosis and treatment of parental breast cancer, and to identify culturally sensitive ways to recruit and sustain participation of this vulnerable population in intervention programs. Methods: Three qualitative focus groups which were part of a larger study were conducted with 12 African‐American youth between the ages of 11 and 18, currently coping with parental breast cancer from the Northeastern part of the United States. Interviews were audio‐taped and transcribed verbatim, and analyzed using content analysis. Results: African‐American youth described fear and uncertainty about the mortality of their parent, their unpredictable future, and discomfort in negotiating breast cancer's relationship with the entire family. Four primary themes emerged which were coping with cancer, it affects us too, changes in family functioning, and growth through pain. African‐American youth described feeling overlooked by their families and oncology staff treating their parents, often being in the role of protecting their parents physically and emotionally. Conclusions: This study suggests that clinicians can improve the care of African‐American breast cancer patients and their adolescent children by being more family‐centered. Adolescents need more developmentally appropriate preparation for the family changes likely to occur when a parent is diagnosed and treated for breast cancer. Developing a support group comprised of other youth coping with parental breast cancer from diagnosis throughout treatment was described as a preferred intervention to promote a shared understanding in order to overcome feelings of isolation, worry, and fear. Copyright © 2010 John Wiley & Sons, Ltd.     

Psychosocial issues related to sexual functioning among African‐American prostate cancer survivors and their spouses

Objective: Focus on cancer survivorship and quality of life (QOL) is a growing priority. The aim of this study was to identify and describe the most salient psychosocial concerns related to sexual functioning among African‐American (AA) prostate cancer survivors and their spouses. Methods: Twelve AA prostate cancer survivors and their spouses participated in semi‐structured individual interviews. The interviews assessed couples' experiences with psychosocial adjustment and sexual functioning posttreatment for localized prostate cancer. The data were analyzed using the constant comparison method and content analysis. Results: In this qualitative study of couples surviving prostate cancer, there were divergent views between the male prostate cancer survivors and their female partners, particularly regarding sexual functioning. For the males, QOL issues emerged as the primary area of concern, whereas survival of their husbands was considered most important among the female spouses. The male respondents expressed unease with the sexual side effects of their cancer treatment, such as erectile dysfunction and decreased sexual desire and satisfaction. Female spouses recognized decreased sexual desire in their partners following treatment, but this was not considered a primary concern. Conclusions: Patients and their spouses may have differing perceptions regarding QOL and the impact of sexual functioning on survivorship. This study points to the need for further research and intervention development to address these domains with a goal to improve QOL. Copyright © 2010 John Wiley & Sons, Ltd.     

An analysis of the psychometric profile and frequency of anxiety and depression in Australian men with prostate cancer

Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to collect data from 195 Australian men who had received a diagnosis of prostate cancer. Analysis was via separate scales and also by combining both scales into a single unit to assess anxiety-depression and then analysing the underlying component structure of that unit. Applying Zung's recommended cutoff scores, 12% of the sample were classified as having clinically significant levels of anxiety and 16% had similar levels of depression. Factor analysis of the combined SAS and SDS indicated four major components which reflected a process of: loss of functional capacity, worthlessness and hopelessness, fear and somatic symptomatology. Implications for the effective assessment and treatment of anxiety and depression in prostate patients are discussed.     

Spirituality and well‐being in cancer patients: a review

Objective: Cancer places many demands on the patient and threatens the person's sense of meaning to life. It has been shown that cancer patients use their spirituality to cope with these experiences. The present literature review summarizes the research findings on the relationship between spirituality and emotional well‐being. Special attention is given to the strength of the research findings. Methods: A literature search was performed in Pubmed and Web of Science. Spirituality does not necessarily coincide with religiosity. Therefore, studies were excluded that focused on religiosity. Forty publications met the inclusion criteria: Twenty‐seven studies that investigated the relationship between spirituality and well‐being, and 13 publications that explored the relationship between meaning in life and well‐being. Results: The majority of the cross‐sectional studies (31 of 36) found a positive association between spirituality and well‐being. The four studies with a longitudinal design showed mixed results. The significance of the findings is challenged, because most spirituality questionnaires contain several items that directly refer to emotional well‐being. Conclusions: Despite that the majority of the studies concluded that spirituality was associated with higher well‐being, no definitive conclusions on this relationship can be drawn due to major methodological shortcomings of these studies. Longitudinal research utilizing spirituality and well‐being measures that do not overlap in content is recommended. Copyright © 2009 John Wiley & Sons, Ltd.