Heparanase promotes bone destruction and invasiveness in prostate cancer

2008 ◽  
Vol 268 (2) ◽  
pp. 252-259 ◽  
Author(s):  
Yu Zhou ◽  
Bin Song ◽  
Wei-jun Qin ◽  
Geng Zhang ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Destruction

scholarly journals The Osteoblastic and Osteoclastic Interactions in Spinal Metastases Secondary to Prostate Cancer

2013 ◽  
Vol 6 ◽  
pp. CGM.S12769 ◽  
Author(s):  
Sathana Dushyanthen ◽  
Davina A.F. Cossigny ◽  
Gerald M.Y. Quan
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Molecular Mechanisms ◽  
Spinal Metastases ◽  
Bone Destruction ◽  
Cord Compression ◽  
Intractable Pain ◽  
Critical Pathway ◽  
Functional Roles ◽  
High Propensity

Prostate cancer (PC) is one of the most common cancers arising in men and has a high propensity for bone metastasis, particularly to the spine. At this stage, it often causes severe morbidity due to pathological fracture and/or metastatic epidural spinal cord compression which, if untreated, inevitably leads to intractable pain, neurological deficit, and paralysis. Unfortunately, the underlying molecular mechanisms driving growth of secondary PC in the bony vertebral column remain largely unknown. Further investigation is warranted in order to identify therapeutic targets in the future. This review summarizes the current understanding of PC bone metastasis in the spine, highlighting interactions between key tumor and bone-derived factors which influence tumor progression, especially the functional roles of osteoblasts and osteoclasts in the bone microenvironment through their interactions with metastatic PC cells and the critical pathway RANK/RANKL/OPG in bone destruction.

Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases

2012 ◽  
Vol 08 (02) ◽  
pp. 94 ◽  
Author(s):  
Neal Shore ◽  
Carsten Goessl ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Comprehensive Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Efficacy Analysis ◽  
Castration Resistant ◽  
Skeletal Complications

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.

scholarly journals Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases

2016 ◽  
Vol 478 (1) ◽  
pp. 154-161
Author(s):  
Kenta Watanabe ◽  
Tsukasa Tominari ◽  
Michiko Hirata ◽  
Chiho Matsumoto ◽  
Takayuki Maruyama ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Destruction ◽  
Human Prostate ◽  
Prostaglandin E ◽  
Human Prostate Cancer ◽  
Cancer Metastases

scholarly journals Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Yanju Bao ◽  
Yebo Gao ◽  
Maobo Du ◽  
Wei Hou ◽  
Liping Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Pain ◽  
Structural Damage ◽  
Bone Pain ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Osteoblast Activity ◽  
Mechanical Threshold ◽  
Bone Damage

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere detected in the XZP-treated rats (P<0.05for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4507-LBA4507 ◽  
Author(s):  
K. Fizazi ◽  
M. A. Carducci ◽  
M. R. Smith ◽  
R. Damião ◽  
J. E. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Progression ◽  
Controlled Trial ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

LBA4507 Background: Bone metastases from hormone-refractory (castration-resistant) prostate cancer (CRPC) are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE). Denosumab is a fully human monoclonal antibody against RANKL. This phase III, randomized, double-blind, active-controlled trial compared the efficacy and safety of denosumab vs. zoledronic acid (ZA) in patients with metastatic CRPC. Methods: Patients (n = 1,901) with CRPC and at least 1 bone metastasis, but no prior IV bisphosphonate use, received either SC denosumab 120 mg and IV placebo (n = 950), or SC placebo and IV ZA 4 mg (n = 951) adjusted for creatinine clearance every 4 weeks. All patients were instructed to take supplemental calcium and vitamin D. The primary endpoint was time to first on-study SRE, defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression. Results: Denosumab significantly delayed the time to first on-study SRE compared with ZA, (HR 0.82 ; 95% CI: 0.71, 0.95 ; p = 0.008.) The median time to first on-study SRE was 20.7 mo denosumab vs. 17.1 mo ZA, a difference of 3.6 months. Denosumab also significantly delayed the time to first and subsequent on-study SRE (multiple event analysis) (HR 0.82 ; 95% CI: 0.71, 0.94 ; p = 0.004). Greater suppression of the bone turnover markers uNTx and BSAP occurred in denosumab patients compared with ZA (p < 0.0001 for both). Overall, adverse event (AE) rates (97% each) and serious AEs (63% denosumab, 60% ZA) were similar, irrespective of potential relationship to study drugs. AEs of hypocalcemia were reported in 13% and 6% of denosumab and ZA patients. Osteonecrosis of the jaw occurred in 22 (2.3%) denosumab compared with 12 (1.3%) ZA patients (p = 0.09). Overall survival (HR 1.03 ; 95% CI: 0.91, 1.17 ; p = 0.65) and time to cancer progression (HR 1.06; 95% CI: 0.95, 1.18; p = 0.30) were similar between treatment arms. Conclusions: Denosumab demonstrated superiority over ZA in delaying or preventing SREs in patients with bone metastases from CRPC. Adverse events were consistent in both treatment groups with those previously reported in advanced cancer populations. [Table: see text]

scholarly journals The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Emma Roberts ◽  
Davina A. F. Cossigny ◽  
Gerald M. Y. Quan
Keyword(s):  
Prostate Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumour Cell ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Spinal Metastases ◽  
Bone Destruction ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF) have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

scholarly journals Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

ISRN Urology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Abdullah Demirtas ◽  
Nurettin Sahin ◽  
Mehmet Caniklioglu ◽  
Mustafa Kula ◽  
Oguz Ekmekcioglu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Bone Destruction ◽  
Serum Levels ◽  
Karnofsky Performance Scale ◽  
Acid Therapy ◽  
Before And After ◽  
Hormone Resistant Prostate Cancer

Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (, , resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful.

Sign in / Sign up

Export Citation Format

Share Document