65 research outputs found
BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells
Moving out of the shadows: accomplishing bisexual motherhood
Our qualitative study explored the ways in which bisexual mothers came to identify as such and how they structured their relationships and
parenting within hetero-patriarchal society. The experiences of seven self-identified White bisexual women (aged from 28 to 56-years-old) from
across England and the Republic of Ireland were investigated through semi-structured interviews. Participants’ children were aged 8 months to
28 years old at the time of their interviews. A thematic narrative analysis highlighted the following issues that participants had encountered in
constructing their self-identity: prioritizing children; connecting and disconnecting with others and finessing self-definition; questioning societal
relationship expectations. Nevertheless, participants varied considerably in how each of the themes identified were reflected in their lives, in
particular depending upon each participant’s interpretation of her local social context. Both motherhood and self-identifying as bisexual gave a
sense of meaning and purpose to participants’ life stories, although participants sometimes foregrounded their commitment to their children
even at a personal cost to their bisexual identity. Using three different theoretical perspectives from feminist theory, queer theory and life course
theory, the narratives analysed revealed ways in which bisexual motherhood not only had been influenced both intentionally and unintentionally
by heteronormative expectations but also had directly and indirectly challenged these expectations
Androgen-Regulated Expression of Arginase 1, Arginase 2 and Interleukin-8 in Human Prostate Cancer
BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in North American men. Androgen-deprivation therapy (ADT) accentuates the infiltration of immune cells within the prostate. However, the immunosuppressive pathways regulated by androgens in PCa are not well characterized. Arginase 2 (ARG2) expression by PCa cells leads to a reduced activation of tumor-specific T cells. Our hypothesis was that androgens could regulate the expression of ARG2 by PCa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we demonstrate that both ARG1 and ARG2 are expressed by hormone-sensitive (HS) and hormone-refractory (HR) PCa cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 was more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 were overexpressed. The regulation of arginase expression following androgen stimulation was dependent on the androgen receptor (AR), as a siRNA treatment targeting the AR inhibited both ARG1 and ARG2 overexpression. This observation was correlated in vivo in patients by immunohistochemistry. Patients treated by ADT prior to surgery had lower ARG2 expression in both non-malignant and malignant tissues. Furthermore, ARG1 and ARG2 were enzymatically active and their decreased expression by siRNA resulted in reduced overall arginase activity and l-arginine metabolism. The decreased ARG1 and ARG2 expression also translated with diminished LNCaP cells cell growth and increased PBMC activation following exposure to LNCaP cells conditioned media. Finally, we found that interleukin-8 (IL-8) was also upregulated following androgen stimulation and that it directly increased the expression of ARG1 and ARG2 in the absence of androgens. CONCLUSION/SIGNIFICANCE: Our data provides the first detailed in vitro and in vivo account of an androgen-regulated immunosuppressive pathway in human PCa through the expression of ARG1, ARG2 and IL-8
Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer
LGBTQ parenting post heterosexual relationship dissolution
The chapter examines parenting among sexual and gender minorities post heterosexual relationship dissolution (PHRD). Reviewing the literature around intersecting identities of LGBTQ parents, we consider how religion, race, and socioeconomic status are associated with routes into and out of heterosexual relationships and variation in the lived experience of sexual and gender identity minorities, in particular how LGBTQ parents PHRD feel about being out. Further consideration is given to examining how family relationships change and develop as parental sexual and/or gender identity changes. We also explore the impact of PHRD identity and parenthood on new partnerships and stepfamily experiences. The chapter addresses the reciprocal relationship between research on LGBTQ parenting and policy and legal influences that impact upon the experience of LGBTQ parenting PHRD when custody and access are disputed. Finally, the chapter includes future research directions and implications for practice in an area that has been revitalized in recent years
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