Pamela Russell | Queensland University of Technology (original) (raw)

Papers by Pamela Russell

Clinical & Experimental Metastasis, 2005

Molecular changes are vital for the development of prognostic markers and therapeutic modalities ... more Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.

Cancer Biology & Therapy, 2008

Clinical Cancer Research, 2009

Proliferation and maintenance of both normal and prostate cancer (PCa) cells is highly regulated ... more Proliferation and maintenance of both normal and prostate cancer (PCa) cells is highly regulated by steroid hormones, particularly androgens, and the extracellular environment. Herein, we identify the secretion of CD9 positive extracellular vesicles (EV) by LNCaP and DUCaP PCa cells in response to dihydrotestosterone (DHT) and use nano-LC–MS/MS to identify the proteins present in these EV. Subsequent bioinformatic and pathway analyses of the mass spectrometry data identified pathologically relevant pathways that may be altered by EV contents. Western blot and CD9 EV TR-FIA assay confirmed a specific increase in the amount of CD9 positive EV in DHT-treated LNCaP and DUCaP cells and treatment of cells with EV enriched with CD9 after DHT exposure can induce proliferation in androgen-deprived conditions. siRNA knockdown of endogenous CD9 in LNCaPs reduced cellular proliferation and expression of AR and prostate specific antigen (PSA) however knockdown of AR did not alter CD9 expression, also implicating CD9 as an upstream regulator of AR. Moreover CD9 positive EV were also found to be significantly higher in plasma from prostate cancer patients in comparison with benign prostatic hyperplasia patients. We conclude that CD9 positive EV are involved in mediating paracrine signalling and contributing toward prostate cancer progression.

Journal of Cancer Science & Therapy, 2011

Cancer Immunology Immunotherapy, 1995

Cancer Gene Therapy, 2002

Faculty of Health Institute of Health and Biomedical Innovation, 2012

ABSTRACT Over 20,000 Australian men are diagnosed with prostate cancer (PC) with more than 3500 d... more ABSTRACT Over 20,000 Australian men are diagnosed with prostate cancer (PC) with more than 3500 deaths/year from this disease. Worldwide, 910,000 cases were recorded in 2008, accounting for 14% of men's cancer, and these figures are predicted to reach 1.7 million by 2030. Early PC is treated by surgery or radiation; androgen depletion therapy (ADT) is subsequently used for those who fail treatment, as PC is androgen regulated. Among these, 25–40% of cases develop castrate-resistant PC (CRPC) with a rising PSA, an androgen-regulated gene, despite low androgen levels in the serum. The underlying mechanisms for progression to CRPC are complex. PC cells that survive ADT arrest adapt to a low-androgen environment through various mechanisms, which maintain androgen receptor (AR) signaling and continue to proliferate. The chemotherapeutic drug, docetaxel, is commonly used to treat CRPC patients in the clinic, but ~30% of patients who receive docetaxel therapy relapse and suffer from severe side effects. Biomarkers, which could define whether patients will respond to ADT and drug treatments, are needed. We believe that exosomes may provide novel biomarkers that will alter with treatment, potentially providing markers that reflect PC progression and drug-resistant disease. We investigated the effects of DHT treatment on exosome secretion using AR positive LNCaP and 22RV1 cell lines as an in vitro PC model. DHT changes the protein profile of exosomes isolated from both cell lines, implying that in PC, the AR plays a role in selecting the content of exosome and confirming that exosome analysis has the potential to provide novel biomarkers for PC progression and drug resistance. Funded by: Department of Defense US Army Prostate Cancer Program Postdoctoral Training Award, and Queensland University of Technology DOI: 10.3402/jev.v1i0.18182

School of Biomedical Sciences Faculty of Health Institute of Health and Biomedical Innovation, 2012

Three new cases of placental candidiasis are reported. Two were associated with fetal cutaneous c... more Three new cases of placental candidiasis are reported. Two were associated with fetal cutaneous candidiasis and one with fetal systemic candidiasis. The systemic case was associated with an intrauterine contraceptive device. Infection of the placenta results in small 'granulomata' under the surface of the cord and a diffuse chorioamnionitis of the membranes and chorionic plate. In reviewing the 24 previously reported cases it can be seen that systemic. Candida infection of the fetus results in prematurity and death, infection can occur across intact membranes, and systemic candidiasis in the fetus is likely to be associated with an intrauterine device.

The American Journal of Pathology, Feb 1, 1994

An experimental system is described in which coronary arteries of mouse hearts transplanted heter... more An experimental system is described in which coronary arteries of mouse hearts transplanted heterotopically develop obstructive lesions by 4 weeks. Transient immunosuppression permits graft survival. Donor/recipient antigenic differences may be either class I or class II major histocompatibility antigens (H-2) or non-H-2 antigens. An infiltrate including CD4+ and CD8+ T lymphocytes and macrophages concentrates early in the intima and adventitia of larger coronary arteries, with little in the myocardium. Subsequently, the intima expands with cells of donor origin and the infiltrate invades the media. Endothelial and intimal cells express ICAM-1, leukocytes LFA-1: Endothelium expresses class I, but not class II, antigens. As class II disparity alone suffices, the endothelium can apparently be an indirect target of immune injury. We propose that graft atherosclerosis is T cell initiated and elicited by heterogeneous antigens in the endothelium or media. It is separable from rejection of the myocardium.