WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: We investigated the role of estradiol (E2) on cell growth in estrogen-sensitive or estrogen-insensitive ovarian cancer cell lines. Real-time (RT)-PCR and western blotting were used to examine the expression of WFDC2 at RNA and protein levels. Growth traits of cells transfected with WFDC2-shRNA or blank control were assessed using MMT arrays. Cell apoptosis was analyzed using annexin V-FITC/PI and flow cytometry. Estrogen receptor expression was evaluated using RT-PCR and flow cytometry. Apoptosis-related proteins induced by E2 directly and indirectly were determined using an antibody array comparing cells transfected with WFDC2- shRNA or a blank control. RESULTS: High-dose (625 ng/ml) E2 increased the expression of WFDC2 in HO8910 cells at both the mRNA and protein levels. However, E2 had no effect on WFDC2 expression in estrogen-insensitive SKOV3 cells. Of interest, knockdown of WFDC2 enabled a considerable estrogen response in SKOV3 cells in terms of proliferation, similar to estrogen-responsive HO8910 cells. This transformation of SKOV3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor beta (ERß) and an effect on cell apoptosis under E2 treatment by regulating genes related to cell proliferation and apoptosis. CONCLUSIONS: We postulate that increased WFDC2 expression plays an important role in altering the estrogen pathway in ovarian cancer, and the identification of WFDC2 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-015-0210-y) contains supplementary material, which is available to authorized users

Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer

Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-xL, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic β-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-xL upon exogenous over-expression

Mothers' accounts of their stillbirth experiences and of their subsequent relationships with their living infant:an interpretative phenomenological analysis

BACKGROUND: Due to contradictory findings regarding the effects of seeing and holding stillborn infants on women's worsening mental health symptoms, there is a lack of clear of guidance in stillbirth bereavement care. Although some current research examines this phenomenon we are still not certain of the meaning of such experiences to women and what effects there may be on her subsequent parenting. Thus the present study focuses on the meaning of the stillbirth experience to women and its influence on the subsequent pregnancy and subsequent parenting from the mothers' own experiences. METHODS: A purposive sample of six women who experienced a stillbirth during their first pregnancy and who then went on to give birth to a living child after a further pregnancy, took part in email interviews, providing rich and detailed experiential narratives about both the stillbirth itself, and their relationship with their living child. An Interpretive Phenomenological Analysis was carried out in order to focus on mothers making sense of such experiences. RESULTS: Analysis of written accounts led to the development of three overarching themes. In 'Broken Canopy', 'How This Happened' and 'Continuing Bonds', their accounts revealed an ongoing process where women accepted a new 'unsafe' view of the world, re-evaluated their view of self and others, and established relationships with both the deceased and the living infant. CONCLUSIONS: This study provided an insight into the stillbirth experience of mothers and its meaning to them with an existential focus. Typically the mother struggled with the contradictory process of accepting the existence of her deceased baby (this baby once lived) while being aware of the nonexistence (this baby). Meeting the dead baby was a crucial point at which the mother started processing her grief. The importance of individual differences in dealing with stressful situations was highlighted in terms of attachment strategies. Subsequent parenting experiences of mothers were very much influenced by their own previous experiences. Although some mothers managed to integrate this trauma into their life some remained very concerned and anxious about future and this anxiety then translated into their parenting experiences

Bereavement, post-traumatic stress and post-traumatic growth: through the lenses of positive psychology

Background: During the past decades we have learned a lot about the psychopathology that can be triggered from adversity, but our knowledge of the qualities developed and processes experienced by people who remain healthy despite having gone through trauma has been limited. A proposed area within positive psychology is the psychology of loss. Psychology of loss emphasizes the study of healthy individuals, the resources they use for adapting to loss, and the ways in which they can transform their losses into personal growth and strength. Under the theoretical umbrella of positive psychology, the construct of post-traumatic growth has also received increased scholarly attention in recent years. Post-traumatic growth is a concept and a construct that reflects the ‘positive psychological change experienced as a result of the struggle with highly challenging life circumstances’ (Tedeschi & Calhoun, ). Numerous empirical studies have described the phenomenon after various traumas, including traumatic bereavement, even among children and adolescents (Kilmer et al., ). Objective: The qualitative study presented was conducted in the UK, where eight women were interviewed after losing their first child perinatally. This type of bereavement constitutes a traumatic loss and although there is a plethora of research focusing on the resulting parental psychopathology, research on adaptive grief resolution and post-traumatic growth is scarce. Method: The research question was ‘How mothers experience personal growth after a perinatal loss’ and the research methodology employed was interpretative phenomenological analysis (Smith, Flowers, & Larkin, ). Results: The analysis revealed four superordinate themes. The first mainly presented the traumatic quality of this type of bereavement and included subthemes such as iatrogenic psychological trauma, while the second presented the multiple losses involved with emerging themes on the amputated object relationship, the socially unrecognized maternal identity and the threatened reproductive ability. The third superordinate theme presented all the coping mechanisms that were activated by participants to work through their loss; emerging themes were rumination and disillusionment, oscillating between action and avoidance, religious and spiritual coping, and the quality of social support as a catalyst. The fourth superordinate theme presented the positive changes that came as a consequence of the experience and their efforts to psychologically survive the loss. The subthemes that emerged in last superordinate theme were growth as an affirmation of the baby’s importance; growth as an outcome of the awareness of personal vulnerability; transformations in self-perception: self-worth and self-efficacy; transformations in perception and attitude: appreciation of life and changed priorities; and transformations in relationships: empathy and companionship. Conclusions: The research findings suggest that following this traumatic loss, mothers, struggling with distress and anguish, can also experience positive transformations. The possible role of counselling psychologists and psychotherapists in this journey of personal positive transformation of bereaved individuals should be further explored and enhanced

Abduction of Children by Their Parents: A Psychopathological Approach to the Problem in Mixed-Ethnicity Marriages

Aim: Child abduction by one parent and their transport to a foreign country is increasing worldwide but has not received adequate scientific interest. When inter-marital relationships reach the point of break-up and divorce, one of the parents abducts his/her child/children. Method: Records of forty seven (47) cases of inter family abduction that took place in 2007 in Greece were obtained. The majority of cases concerned relocation of children in a foreign country. A special inventory was developed for data collection. This consisted of three distinctive parts, for the father, the mother, or the abducted child. Results: Results showed that a typical abductive mother is of non Greek nationality, more likely of having psychiatric symptoms, without indication of substance abuse and no signs of violent behavior. Abductive fathers are of Greek nationality, less likely of having psychiatric symptoms, no substance abuse, and tend to exhibit violent behavior. Legal resolution of these cases and repatriation takes very long adding to the child and family’s distress. Conclusions: Child abduction is associated with cases of dissolved marriages. Domestic violence is frequent. Child abduction cases takes on average 3.5 years to be resolved, a phenomenon that has obvious implications on the mental health of the children and the parents involved