Loss of Let-7 Up-Regulates EZH2 in Prostate Cancer Consistent with the Acquisition of Cancer Stem Cell Signatures That Are Attenuated by BR-DIM

The emergence of castrate-resistant prostate cancer (CRPC) contributes to the high mortality of patients diagnosed with prostate cancer (PCa), which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs). Recent studies have shown that deregulated expression of microRNAs (miRNAs) contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2), a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3′UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3′-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM) up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact

Healing through culturally embedded practice: an investigation of counsellors’ and clients’ experiences of Buddhist Counselling in Thailand

This thesis is concerned with an exploration of counsellors’ and clients’ lived experiences of Buddhist Counselling, an indigenous Buddhist-based counselling approach in Thailand. Over the past decade, Buddhist Counselling has received a growing interest from Thai counselling trainees and practitioners, and it has also expanded to serve Thai people in various settings. Research on Buddhist Counselling is very limited and most of the existing studies in the field have focused on measuring the effectiveness of the approach. While these studies have consistently indicated the positive effects of Buddhist Counselling on psychological improvement across several population groups, the significant questions of how Buddhist Counselling brings about such outcome and how it is experienced are still largely unanswered. Moreover, existing research is concentrated much more on clients’ views than counsellors’ views, although counsellors’ views of their counselling practice can also serve as a knowledge base of the field. This thesis thus sets out to contribute to rectifying this omission by exploring Buddhist Counselling from the perspectives of both counsellors and clients. The thesis is based on two qualitative studies. The first study addressed Buddhist Counselling from the perspective of five counsellors through a focus group and semi-structured interviews. The second study explored Buddhist Counselling from the perspective of three clients, using two semi-structured interviews with each of them. All data received were analysed using interpretative phenomenological analysis (IPA). The study reveals counsellors’ and clients’ overall positive experience of engaging in Buddhist Counselling. Central to the accounts of the counsellors are the following perceptions: that their practice of Buddhist Counselling is culturally congruent with the existing values and beliefs of both themselves and their clients; that their personal and professional congruence is key to their therapeutic efficacy; and that they enhance such congruence through their application of Buddhist ideas and practices in their daily lives. Key to the clients’ accounts is their emphasis on the significant roles of the counsellors’ Buddhist ideas and personal qualities, and of their religious practices in facilitating healing and change. Key shared findings from both studies reveal that the participants’ accounts of their cultural background and their experiences of Buddhist Counselling are intertwined. Adopting hermeneutics to address this intertwinement, I reveal the cultural and moral dimensions underlying the practice of Buddhist Counselling. Based on such revelation, I suggest that Buddhist Counselling in particular, as well as psychotherapy in general, should be better understood as a historically situated, culturally bound, and morally constituted activity of people who are concerned with improving the quality of their lives and their community, rather than the transcultural and merely relational work of morally-neutral practitioners