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Li Y.,Cancer Care Center | Li Y.,University of New South Wales | Cozzi P.J.,University of New South Wales
Medicinal Research Reviews | Year: 2010

It is becoming increasingly clear that angiogenesis plays a crucial role in prostate cancer (CaP) survival, progression, and metastasis. Tumor angiogenesis is a hallmark of advanced cancers and an attractive treatment target in multiple solid tumors. By understanding the molecular basis of resistance to androgen withdrawal and chemotherapy in CaP, the rational design of targeted therapeutics is possible. This review summarizes the recent advancements that have improved our understanding of the role of angiogenesis in CaP metastasis and the potential therapeutic efficacy of inhibiting angiogenesis in this disease. Current therapeutic options for patients with metastatic hormone-refractory CaP are very limited. Targeting vasculature is a developing area, which shows promise for the control of late stage and recurrent CaP disease and for overcoming drug resistance. We discuss angiogenesis and its postulated mechanisms and focus on the regulation of angiogenesis in CaP progression and the therapeutic beneficial effects associated with targeting of the CaP vasculature to overcome the resistance to current treatments and CaP recurrence. © 2009 Wiley Periodicals, Inc.

Introduction The purpose of this study was to evaluate the cardiac dosimetry delivered before and after routine 3D CT whole-breast radiotherapy planning, including cardiac contouring and the relevance of a 15-mm maximum myocardial depth (MMD) planning tolerance threshold. Methods The PULp FICTion study permitted cardiac dosimetry comparisons for 140 patients (70 in the 'before-contouring era' (BC) and 70 in the 'post-contouring era' (PC) ). Comparisons were made of MMD and dosimetry for whole heart, anterior myocardium and left anterior descending (LAD)/coronary artery (overall, superior and inferior) by contouring era. Results The MMD mean was 15.6 mm (range 1-40). If the internal mammary chain (IMC) was treated, the MMD increased from 15 to 27.7 mm (P < 0.0001). Excluding IMC patients revealed no difference in MMD between conservation and mastectomy (14.9 vs 17.4, P = 0.3), boost and no boost (14.5 vs 15.5, P = 0.41) or BC and PC (15.7 vs 14.5. P = 0.33) and no differences related to treating clinician, anthracycline use or age. Only in potentially low-risk patients defined as not requiring IMC or boost treatment was there a difference in MMD by era, with 17.7 mm (1-40) in the BC era and 13.9 mm (1-31) mm in the PC era (P = 0.013). Inferior LAD mean doses increased from 49% to 84% of the prescribed breast dose when MMD was >15 mm, and the proportion of patients with a mean dose <40% of the prescribed breast dose fell from 48% to 8%. Conclusion Changes in cardiac dosimetry associated with routine cardiac contouring have initially been minor and restricted to low-risk patients. A 15-mm MMD reasonably represents a transition from low mean distal LAD doses to substantial doses. © 2014 The Royal Australian and New Zealand College of Radiologists.

Huo Y.R.,University of New South Wales | Richards A.,University of New South Wales | Liauw W.,Cancer Care Center | Morris D.L.,University of New South Wales
European Journal of Surgical Oncology | Year: 2015

Purpose Emerging evidence suggests that hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) shows a survival benefit over CRS alone for patients with epithelial ovarian carcinoma (EOC). This systematic review and meta-analysis will assess the safety and efficacy of HIPEC with CRS for EOC. Design Searches of five databases from inception to 17/02/15 was performed. Clinical outcomes were synthesised, with full tabulation of results. Results A total of 9 comparative studies and 28 studies examining HIPEC + CRS for primary and/or recurrent EOC were included. Meta-analysis of the comparative studies showed HIPEC + CRS + chemotherapy had significantly better 1-year survival compared with CRS + chemotherapy alone (OR: 3.76, 95% CI 1.81-7.82). The benefit of HIPEC + CRS continued for 2-, 3-, 4-, 5- and 8-year survival compared to CRS alone (OR: 2.76, 95% CI 1.71-4.26; OR: 5.04, 95% CI 3.24-7.85; OR: 3.51, 95% CI 2.00-6.17; OR: 3.46 95% CI 2.19-5.48; OR: 2.42, 95% 1.38-4.24, respectively). Morbidity and mortality rates were similar. Pooled analysis of all studies showed that among patients with primary EOC, the median, 1-, 3-, and 5-year overall survival rates are 46.1 months, 88.2%, 62.7% and 51%. For recurrent EOC, the median, 1-, 3-, and 5-year overall survival rates are 34.9 months, 88.6%, 64.8% and 46.3%. A step-wise positive correlation between completeness of cytoreduction and survival was found. Conclusion The addition of HIPEC to CRS and chemotherapy improves overall survival rates for both primary and recurrent EOC. © 2015 Elsevier Ltd.

Li Y.,Cancer Care Center | Li Y.,University of New South Wales | Cozzi P.J.,University of New South Wales | Russell P.J.,University of New South Wales | Russell P.J.,Oncology Research Center
Medicinal Research Reviews | Year: 2010

Prostate cancer (CaP) is one of the most prevalent malignant diseases among men in Western countries. There is currently no cure for metastatic castrate-resistant CaP, and median survival for these patients is about 18 months; the high mortality rate seen is associated with widespread metastases. Progression of CaP from primary to metastatic disease is associated with several molecular and genetic changes that can affect the expression of specific tumor-associated antigens (TAAs) or receptors on the cell surface. Targeting TAAs is emerging as an area of promise for controlling late-stage and recurrent CaP. Several reviews have summarized the progress made in targeting signaling pathways for CaP but will not be discussed here. We describe some important CaP TAAs. These include prostate stem-cell antigen, prostate-specific membrane antigen, MUC1, epidermal growth factor receptor, platelet-derived growth factor and its receptor, urokinase plasminogen activator and its receptor, and extracellular matrix metalloproteinase inducer. We summarize recent advancements in our understanding of their role in CaP metastasis, as well as potential therapeutic options for targeting CaP TAAs. We also discuss the origin, identification, and characterization of prostate cancer stem cells (CSCs) and the potential benefits of targeting prostate CSCs to overcome chemoresistance and CaP recurrence. © 2009 Wiley Periodicals, Inc.

Chua T.C.,University of New South Wales | Chong C.H.,University of New South Wales | Liauw W.,Cancer Care Center | Zhao J.,University of New South Wales | Morris D.L.,University of New South Wales
Annals of Surgery | Year: 2012

BACKGROUND: The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. METHODS: Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. RESULTS: A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P < 0.001, P = 0.001), CA125 (P = 0.004, P < 0.001), CA199 (P < 0.001, P < 0.001). On multivariate analysis, there were no independent predictors of OS. PFS was independently associated with the presence of lymph node metastasis (P = 0.02), CA199 > 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. CONCLUSIONS: The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment. © 2012 Lippincott Williams & Wilkins, Inc.

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