scholarly journals Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94834-94849 ◽  
Author(s):  
Yun Ye ◽  
Su-Liang Li ◽  
Yue-Yun Ma ◽  
Yan-Jun Diao ◽  
Liu Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Osteoblastic Metastasis ◽  
Osteoblast Activity

Osteoprotegerin expression during the micro- and macrometastatic phases of the osteoblastic metastasis in prostate cancer: therapeutic implications

2013 ◽  
Vol 17 (12) ◽  
pp. 1395-1403 ◽  
Author(s):  
Spyros G Pneumaticos ◽  
Anthos Christofides ◽  
Eliona Gkioka ◽  
Theodoros Kalogeropoulos ◽  
Pavlos Msaouel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Implications ◽  
Osteoblastic Metastasis

scholarly journals Dual PI3 K/mTOR inhibition reduces prostate cancer bone engraftment altering tumor-induced bone remodeling

Tumor Biology ◽  
2018 ◽  
Vol 40 (4) ◽  
pp. 101042831877177 ◽  
Author(s):  
Andrea Mancini ◽  
Alessandro Colapietro ◽  
Simona Pompili ◽  
Andrea Del Fattore ◽  
Simona Delle Monache ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Therapeutic Potential ◽  
Disease Free Survival ◽  
Bone Lesions ◽  
Metastatic Progression ◽  
Mtor Inhibition ◽  
Osteoblast Activity

Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions. We observed that X480 both inhibited the primary growth of subcutaneous tumors generated by PC3 and 22rv1 cells and reduced bone spreading of PCb2, a high osteotropic PC3 cell derivative. In metastatic bone, X480 inhibited significantly the growth and osteolytic activity of PC3 cells as observed by intratibial injection model. X480 also increased the bone disease-free survival compared to untreated animals. In vitro experiments demonstrated that X480 was effective in counteracting osteoclastogenesis whereas it stimulated osteoblast activity. Our report provides novel information on the potential activity of PI3 K/Akt inhibitors on the formation and progression of prostate cancer bone metastases and supports a biological rationale for the use of these inhibitors in castrate-resistant prostate cancer patients at high risk of developing clinically evident bone lesions.

Measurement of DKK1 and FRP in breast and prostate cancer patients with bone metastases: Impact of zoledronic acid (ZA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19659-19659
Author(s):  
T. Helsten ◽  
M. Corr ◽  
J. E. Mortimer
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Post Treatment ◽  
Bone Homeostasis ◽  
Breast Cancer Patients ◽  
Bone Specific Alkaline Phosphatase ◽  
Osteoblast Activity ◽  
Breast And Prostate Cancer

19659 Background: Bone metastases produce an imbalance in osteoblast and osteoclast activity. While metastases from prostate cancer are osteoblastic, metastases from breast cancer may be osteolytic, osteoblastic or mixed. The wnt/frizzled pathway is involved in maturation of osteoblasts and in adult bone homeostasis. We explored the wnt antagonists dickkopf (DKK1) and frizzled related protein (FRP) as potential biomarkers in bone metastasis after ZA treatment. Methods: This is a pilot cohort study in bisphosphonate naive breast and prostate cancer patients with bone metastases. Cancer therapy was not specified. Patients received 2 monthly doses of ZA 4 mg IV. Pre- and post-treatment (day 60) sera were collected for measurement of FRP and DKK1, along with IL-6, calcium, creatinine and bone-specific alkaline phosphatase (BAP, a marker of osteoblast activity). Primary endpoint: mean change in FRP and DKK1; Secondary endpoints: correlation of biomarkers with each other and comparison of breast vs. prostate cancer patients. Biomarkers were measured using standard ELISA assays. Statistics: comparison of means = student t-test, correlation coefficients = Pearson. Results: Mature data from 14 patients are reported here, 9 with breast and 5 with prostate cancer. Mean age = 61 years (range 42–89). Two breast cancer patients were premenopausal. One prostate and 3 breast cancer patients received chemotherapy; all others were treated hormonally. After ZA, calcium decreased in all patients (p = 0.09). BAP decreased in all but 1 breast and 1 prostate cancer patient (mean decrease 20.0, p = 0.16). IL-6 was undetectable in most patients. FRP decreased in all but 4 patients (mean decrease 6.2, p = 0.13). There was no discernable pattern for DKK1. Pre-treatment DKK1 correlated with FRP (p = 0.01, r2 = 0.39), but there was no correlation post-treatment. Post-treatment DKK1 correlated with both serum calcium (p = 0.04, r2 = 0.49) and BAP (p = 0.005, r2 = 0.65). There was no difference between breast and prostate cancer patients. Conclusions: It is feasible to measure DKK1 and FRP in patients with malignant bone disease. Treatment with ZA has measurable effects upon these and other serum markers. Further studies with more patients are needed to evaluate their potential as biomarkers. No significant financial relationships to disclose.

scholarly journals Systemic Alterations of Wnt Inhibitors in Patients with Prostate Cancer and Bone Metastases

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Stefan Aufderklamm ◽  
Jörg Hennenlotter ◽  
Phillip Leidenberger ◽  
Steffen Rausch ◽  
Andrea Hohneder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Study Cohort ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Osteoblast Activity ◽  
Osteolytic Metastases ◽  
Post Hoc

Purpose. Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods. The study cohort (N=143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1). Serum levels of DKK-1 and sclerostin were measured by enzyme-linked immunosorbent assay. Results were compared using the Kruskal-Wallis tests; post hoc analysis was performed using the Tukey-Kramer test. Results. Mean DKK-1 levels in patients with BPH (2809.4 pg/ml) (p<0.001) as well as PC cM1 (2575.5 pg/ml) (p=0.001) were significantly higher than in patients with PC cN0 cM0 (1551.8 pg/ml). Among PC cM1 patients, median DKK-1 levels were significantly lower in patients with castration-resistant disease compared to those with hormone-sensitive PC (p=0.02); in contrast, sclerostin concentrations were elevated (p=0.04). DKK-1 correlated with PSA in the cM1 group (p=0.03) and sclerostin correlated with PSA in the PC group (0.01). Conclusions. DKK-1 is involved in the progression of PC. DKK-1-mediated inhibition of osteoblasts, which contributes to tumor progression and osteolytic metastases, may also play a role in the development of metastases with osteoblastic features. The use of DKK-1 antibodies should be considered for studies including metastatic PC patients.

Severe hypocalcemia due to osteoblastic metastasis of prostate cancer

2017 ◽  
Vol 148 (6) ◽  
pp. 287-288
Author(s):  
Marta Diéguez Felechosa ◽  
Julio Noval Menéndez ◽  
Laura Manjón Miguelez
Keyword(s):  
Prostate Cancer ◽  
Osteoblastic Metastasis

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.

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