scholarly journals Molecular Regulation of Bone Metastasis Pathogenesis

2018 ◽  
Vol 46 (4) ◽  
pp. 1423-1438 ◽  
Author(s):  
Meng-Yu Wu ◽  
Chia-Jung Li ◽  
Giou-Teng Yiang ◽  
Yeung-Leung Cheng ◽  
Andy Po-Yi Tsai ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Bone Metastases ◽  
Bone Fractures ◽  
Suppressor Cells ◽  
Distant Metastases ◽  
Cord Compression ◽  
Osteolytic Lesions ◽  
Parathyroid Hormone Related Protein ◽  
Osteoprotegerin Ligand

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

scholarly journals Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study

2019 ◽  
Vol 180 (5) ◽  
pp. 311-320 ◽  
Author(s):  
Alfredo Berruti ◽  
Rossella Libè ◽  
Marta Laganà ◽  
Hester Ettaieb ◽  
Mohamad Anas Sukkari ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Bone Metastases ◽  
Adrenocortical Carcinoma ◽  
Bone Fractures ◽  
The United States ◽  
Cord Compression ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
Improve Patient

Introduction Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent. Objective The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis. Methods This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States. Results Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19–4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range. Conclusion Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.

scholarly journals Bone Metastasis Pain, from the Bench to the Bedside

2019 ◽  
Vol 20 (2) ◽  
pp. 280 ◽  
Author(s):  
Federica Aielli ◽  
Marco Ponzetti ◽  
Nadia Rucci
Keyword(s):  
Spinal Cord ◽  
Bone Metastasis ◽  
Bone Fractures ◽  
Ex Vivo ◽  
Life Quality ◽  
Cord Compression ◽  
Cellular Mechanisms ◽  
Oncologic Patients ◽  
Virtuous Cycle

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapons. This review’s purpose is to discuss the molecular and cellular mechanisms that lead to CIBP, including how cancer cells convert the bone “virtuous cycle” into a cancer-fuelling “vicious cycle”, and how this leads to the release of molecular mediators of pain, including protons, neurotrophins, interleukins, chemokines and ATP. Preclinical tests and assays to evaluate CIBP, including the incapacitance tester (in vivo), and neuron/glial activation in the dorsal root ganglia/spinal cord (ex vivo) will also be presented. Furthermore, current therapeutic options for CIBP are quite limited and nonspecific and they will also be discussed, along with up-and-coming options that may render CIBP easier to treat and let patients forget they are patients.

PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21039-e21039
Author(s):  
Charity L. Washam ◽  
Stephanie D. Byrum ◽  
Kim Leitzel ◽  
Ali M. Suhail ◽  
Allan Lipton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
Parathyroid Hormone Related Protein ◽  
Increased Risk ◽  
Breast Cancer Bone Metastasis

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p < 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.

Clinical Usefulness of Bisphosphonates in Oncology: Treatment of Bone Metastases, antitumoral Activity and Effect on Bone Resorption Markers

2007 ◽  
Vol 22 (1) ◽  
pp. 24-33 ◽  
Author(s):  
A. Verì ◽  
M.R. D'Andrea ◽  
P. Bonginelli ◽  
G. Gasparini
Keyword(s):  
Bone Metastases ◽  
Advanced Disease ◽  
Cord Compression ◽  
Antitumoral Activity ◽  
Pathological Fractures ◽  
Antiangiogenic Activity ◽  
Treatment And Prevention ◽  
Oncology Treatment ◽  
Skeletal Related Events

The present article overviews the role of bisphosphonates for the treatment and prevention of bone metastases and their antiangiogenic effects and antitumoral activity. The skeleton is a frequent and clinically relevant site of metastasis in cancer patients. The major events related to bone metastases include bone pain, bone loss, hypercalcemia, spinal cord compression, and fractures. On the basis of their radiographic features, bone metastases are classified as osteoblastic, osteoclastic, or mixed. The primary goals of treatment of bone metastases are reduction of the risk of pathological fractures and other skeletal-related events, and pain control. Bisphosphonates are used to prevent pathological fractures by inhibition of osteoclasts. Recent studies suggest that bisphosphonates have some direct antitumoral activity, mainly mediated through the blockade of angiogenic pathways. Further clinical studies are needed to determine the optimal treatment duration, timing and schedule of bisphosphonates, assess their role as adjuvant therapy for the prevention of bone metastases, and establish their antiangiogenic activity in association with standard cytotoxic and hormonal drugs for treatment of patients with advanced disease.

scholarly journals Radionuclide Bone Scintigraphy: An Interesting Case Report

2015 ◽  
Vol 17 (1) ◽  
pp. 111-115
Author(s):  
Mohana Hossain ◽  
Hosne Ara Rahman ◽  
Mahbubul Haque ◽  
Mahbubur Rahman ◽  
Md Sanowar Hossain ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Eosinophilic Granuloma ◽  
Metastatic Lesion ◽  
Interesting Case ◽  
Whole Body ◽  
Osteolytic Lesions ◽  
Multiple Imaging ◽  
Imaging Results

It is well established that Technetium99mmethylene diphosphonate (Tc99m MDP) whole body bone scintigraphy (WBBS) can demonstrate multiple lesions with increased radiotracer concentration in involved bone. But it is hard to differentiate multiple benign osteolytic lesions from disseminated bone metastases. Even combined with medical history and multiple imaging results, clinical diagnosis of metastatic lesion remains a challenge. This can affect the treatment procedure. Here the role of skeletal scintigraphy in a case of eosinophilic granuloma is evaluated and concluded that additional attention should be given before diagnosing any case as bone metastases. DOI: http://dx.doi.org/10.3329/bjnm.v17i1.22502 Bangladesh J. Nuclear Med. 17(1): 111-115, January 2014

scholarly journals IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Qian Jin ◽  
He Yang ◽  
Zhao Jing ◽  
Wu Hong-hua ◽  
Song Ben-jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bone Metastasis ◽  
Bone Destruction ◽  
Type I ◽  
Erk Pathway ◽  
Osteolytic Lesions ◽  
Osteoclast Precursors ◽  
Metastatic Microenvironment ◽  
Metastatic Sites

Abstract Background Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. Methods In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells Results The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. Conclusion Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

scholarly journals miR-145-5p Mimic Inhibits Bone Metastasis of Prostate Cancer Via the Regulation of Epithelial Mesenchymal Transition

2021 ◽  
Author(s):  
Bingfeng Luo ◽  
Yuan Yuan ◽  
Jian Hou ◽  
Guanming Kuang ◽  
Ping Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Wound Healing ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Western Blotting ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Western Blotting Analysis

Abstract Background: The bone is the most common site of distant metastasis in prostate cancer. However, treatments for the bone metastasis of prostate cancer remain unsatisfactory. MicroRNAs (miRNAs) are small noncoding RNAs that play a variety of critical roles in tumor development and progression. Studies have confirmed that miRNA mimics could regulate the response to therapy in many cancers. Methods: In this study, a set of forty-four miRNAs were reduced in prostate cancer patients with bone metastases by high-throughput sequencing analysis. Wound healing, transwell assays and western blotting analysis were used to explore the role of miRNA mimic in prostate cancer bone metastasis. Results: Further gene ontology and pathway analysis showed that these miRNAs target genes are mainly involved in cellular metabolic process, intracellular membrane-bounded organelle, as well as proteoglycans in cancer and focal adhesion. Therefore, these down-regulated miRNAs may play a key role for prostate cancer bone metastasis treatment, including hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-133a-3p, hsa-miR-222-5p, hsa-miR-204-3p, hsa-miR-145-5p, hsa-miR-3681-5p, hsa-miR-184, hsa-miR-144-3p, hsa-miR-204-5p, and hsa-miR-221-5p. To further investigate the role of these miRNA mimics on prostate cancer bone metastasis, miR-145-5p was randomly selected for validation. Bioinformatics analysis showed that miR-145-5p target genes significantly affected TGF-beta and adherens junction signaling pathway. Wound healing and transwell assays and western blotting analysis revealed that miR-145-5p mimic inhibited proliferation, migration and invasion. Importantly, miR-145-5p mimic increased the expression of E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9. These results revealed that miR-145-5p mimic mediated epithelial mesenchymal transition. Meanwhile, miR-145-5p mimic enhanced the level of caspase 9, which is an important promoter of apoptosis. Conclusions: These results indicate that miR-145-5p mimic could inhibit the progress of prostate cancer bone metastasis via regulation of epithelial mesenchymal transition. In addition, miR-145-5p mimic could induce the apoptosis of prostate cancer cells with bone metastases. In summary, the miR-145-5p mimic is expected to become a novel strategy for the treatment of tumor metastasis.

scholarly journals Early prognostic factors at the time of diagnosis of bone metastasis in patients with bone metastases of differentiated thyroid carcinoma

2016 ◽  
Vol 175 (3) ◽  
pp. 165-172 ◽  
Author(s):  
Yun Mi Choi ◽  
Won Gu Kim ◽  
Hyemi Kwon ◽  
Min Ji Jeon ◽  
Jong Jin Lee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Factors ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Elevated Serum ◽  
Distant Metastases ◽  
Significant Prognostic Factor ◽  
Serum Thyroglobulin ◽  
Significant Difference ◽  
Diagnosis Of Bone Metastasis

Objective Bone is the second most common site of distant metastases from differentiated thyroid cancer (DTC). Patients with bone metastases were associated with poor clinical outcomes; however, their clinical courses are heterogeneous. The aim of this study is to evaluate early prognostic factors of patients with bone metastases from DTC at the time of diagnosis of bone metastasis. Methods This retrospective study included 93 patients with bone metastases from DTC. We defined ‘Pre-RAIT group’ as patients whose bone metastases were detected before initial RAIT. The ‘post-RAIT group’ was defined as patients whose bone metastases were detected after initial RAIT or during the follow-up period. Results Median age was 55.4years, and 55 patients (59%) had papillary thyroid cancer. Patients in the pre-RAIT group (n=32) demonstrated significantly poorer overall survival (OS) (HR=1.86, P=0.04) than those in the post-RAIT group. There was no significant difference in the OS according to the initial RAI avidity among all patients (P=0.18). RAI-avid bone metastases had better OS only in the pre-RAIT group (HR=0.23, P=0.01) but not in the post-RAIT group. In the post-RAIT group, older age (>45years), elevated serum thyroglobulin (Tg) level (>250ng/mL), and the presence of skeletal-related events (SREs) were significantly associated with poor OS. RAI avidity was not a significant prognostic factor in the post-RAIT group (P=0.33). Conclusions Patients whose bone metastases were diagnosed before initial RAIT demonstrate a poorer prognosis. RAI avidity is an early prognostic indicator in the pre-RAIT group. Old age, higher serum Tg levels, and SRE are associated with poor survival outcomes in the post-RAIT group.

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