- Lai, John, Myers, Stephen, Lawrence, Mitchell, Odorico, Dimitri, Clements, Judith
- Authors: Lai, John , Myers, Stephen , Lawrence, Mitchell , Odorico, Dimitri , Clements, Judith
- Date: 2009
- Type: Text , Journal article
- Relation: Molecular Cancer Research Vol. 7, no. 1 (2009), p. 129-141
- Full Text: false
- Reviewed:
- Description: Kallikrein 4 (KLK4) is a member of the human KLK gene family of serine proteases, many of which are implicated in hormone-dependent cancers. Like other KLKs, such as KLK3/PSA and KLK2, KLK4 gene expression is also regulated by steroid hormones in hormone-dependent cancers, although the transcriptional mechanisms are ill defined. Here, we have investigated the mechanisms mediating the hormonal regulation of KLK4 in breast (T47D) and prostate (LNCaP and 22Rv1) cancer cells. We have shown that KLK4 is only expressed in breast and prostate cancers that express the progesterone receptor (PR) and androgen receptor (AR), respectively. Expression analysis in PR- and AR-positive cells showed that the two predominant KLK4 variants that use either TIS1 or TIS2a/b are both up-regulated by progesterone in T47D cells and androgens in LNCaP cells. Two putative hormone response elements, K4.pPRE and K4.pARE at -2419 bp and -1005 bp, respectively, were identified in silico. Electrophoretic mobility shift assays and luciferase reporter experiments suggest that neither K4.pARE nor ∼2.8 kb of the KLK4 promoter interacts directly with the AR to mediate KLK4 expression in LNCaP and 22Rv1 cells. However, we have shown that K4.pPRE interacts directly with the PR to up-regulate KLK4 gene expression in T47D cells. Further, chromatin immunoprecipitation experiments showed a time-dependent recruitment of the PR to the KLK4 promoter (-2496 to -2283), which harbors K4.pPRE. This is the first study to show that progesterone- regulated KLK4 expression in T47D cells is mediated partly by a hormone response element (K4.pPRE) at -2419 bp. (Mol Cancer Res 2009;7(1):129-41)Copyright © 2009 American Association for Cancer Research.
The psychological aftermath of prostate cancer treatment choices : A comparison of depression, anxiety and quality of life outcomes over the 12 months following diagnosis
- Couper, Jeremy, Love, Anthony, Dunai, Judy, Duchesne, G. M., Bloch, Sidney, Costello, Anthony, Kissane, David
- Authors: Couper, Jeremy , Love, Anthony , Dunai, Judy , Duchesne, G. M. , Bloch, Sidney , Costello, Anthony , Kissane, David
- Date: 2009
- Type: Text , Journal article
- Relation: Medical Journal of Australia Vol. 190, no. 7 SUPPL. (2009), p. S86-S89
- Full Text:
- Reviewed:
- Description: Objective: To assess the psychological impact of the different treatments for localised prostate cancer (PCA). Design, participants and setting: Observational, prospective study of consecutive patients with PCA attending clinics in public hospitals and private practices in metropolitan Melbourne between 1 April 2001 and 30 December 2005. Data were collected at initial diagnosis of histologically confirmed localised PCA, and close to the commencement of definitive treatment (Time 1), and 12 months later (Time 2). Patients were stratified according to treatment type (radical prostatectomy [RP], hormone therapy [HT] or other early treatment including radiation therapies [OET]). Patients who elected to undergo active surveillance/ watchful waiting (WW) rather than active treatment were treated as a naturalistic control group. Main outcome measures: Levels of depression and anxiety were assessed by the Brief Symptom Inventory, and physical and psychosocial aspects of health-related quality of life (HRQOL) were assessed by the 36-item Short-Form Health Survey. Results: 211 patients with PCA were recruited; 193 completed the Time 1 questionnaires (38 RP, 56 HT, 38 OET and 61 WW); and 172 completed the Time 2 questionnaires (33 RP, 51 HT, 33 OET and 55 WW). At Time 1, the three active treatment groups all reported greater dysfunction in work role and daily activities compared with the WW group. The RP group also reported worse social and emotional role functioning, while the HT and OET groups reported poorer vitality levels. The HT group reported significantly higher depression scores. At Time 2, the RP and OET groups did not differ from the WW group on either HRQOL or psychological status. By contrast, the HT group reported significantly worse HRQOL (physical functioning, role-physical and vitality domains) and greater psychological distress compared with the WW group. Conclusions: Compared with the other active treatments for localised PCA, HT appears to be associated with poorer HRQOL and greater psychological distress 12 months after commencing treatment.
- Authors: Couper, Jeremy , Love, Anthony , Dunai, Judy , Duchesne, G. M. , Bloch, Sidney , Costello, Anthony , Kissane, David
- Date: 2009
- Type: Text , Journal article
- Relation: Medical Journal of Australia Vol. 190, no. 7 SUPPL. (2009), p. S86-S89
- Full Text:
- Reviewed:
- Description: Objective: To assess the psychological impact of the different treatments for localised prostate cancer (PCA). Design, participants and setting: Observational, prospective study of consecutive patients with PCA attending clinics in public hospitals and private practices in metropolitan Melbourne between 1 April 2001 and 30 December 2005. Data were collected at initial diagnosis of histologically confirmed localised PCA, and close to the commencement of definitive treatment (Time 1), and 12 months later (Time 2). Patients were stratified according to treatment type (radical prostatectomy [RP], hormone therapy [HT] or other early treatment including radiation therapies [OET]). Patients who elected to undergo active surveillance/ watchful waiting (WW) rather than active treatment were treated as a naturalistic control group. Main outcome measures: Levels of depression and anxiety were assessed by the Brief Symptom Inventory, and physical and psychosocial aspects of health-related quality of life (HRQOL) were assessed by the 36-item Short-Form Health Survey. Results: 211 patients with PCA were recruited; 193 completed the Time 1 questionnaires (38 RP, 56 HT, 38 OET and 61 WW); and 172 completed the Time 2 questionnaires (33 RP, 51 HT, 33 OET and 55 WW). At Time 1, the three active treatment groups all reported greater dysfunction in work role and daily activities compared with the WW group. The RP group also reported worse social and emotional role functioning, while the HT and OET groups reported poorer vitality levels. The HT group reported significantly higher depression scores. At Time 2, the RP and OET groups did not differ from the WW group on either HRQOL or psychological status. By contrast, the HT group reported significantly worse HRQOL (physical functioning, role-physical and vitality domains) and greater psychological distress compared with the WW group. Conclusions: Compared with the other active treatments for localised PCA, HT appears to be associated with poorer HRQOL and greater psychological distress 12 months after commencing treatment.
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