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NEWS

Palliative Radiotherapy in Elderly Patients With Bone Metastases Improves Quality of Life
May 20, 2013
In Mouse Model, Imaging Strategy Follows Prostate Cancer Bone Metastasis Response to Cabozantinib
April 22, 2013
Zoledronic Acid Did Not Prevent Bone Metastases in High-Risk Prostate Cancer
April 18, 2013
Cabozantinib Active in Advanced Castration-Resistant Prostate Cancer
December 10, 2012
Metastatic Breast Cancer Cells Diminish Body’s Immune Response
July 26, 2012


 
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Bone Metastases

 
 
REVIEW ARTICLES

Bone-Modifying Agents as Adjuvant Therapy for Early-Stage Breast Cancer
Maria Cristina Figueroa-Magalhães, MD1, Robert S. Miller, MD, FACP2 , October 23, 2012

In this review we describe the current evidence for use of bisphosphonates as part of the adjuvant treatment of patients with early-stage breast cancer.
• Sixty Is the New Forty—or Is It the Other Way Around?
• Can Bone-Targeted Therapy Reduce Recurrence and Improve Survival in Early-Stage Breast Cancer?

Evolution of Treatment Options for Patients With CRPC and Bone Metastases: Bone-Targeted Agents That Go Beyond Palliation of Symptoms to Improve Overall Survival
Kyle O. Rove, MD1, E. David Crawford, MD1 , December 31, 2011

This review will examine agents with potential activity in the palliation and treatment of skeletal metastases of PCa, and will weigh the clinical-outcomes evidence for and against their broad use.
• Managing CRPC: Improving Symptoms, Survival, or Both?
• Are We Trumping Bone Disease in Prostate Cancer?

Early Breast and Prostate Cancer and Clinical Outcomes (Fracture)
Rowan T. Chlebowski, MD, PhD1, Tomoko Tagawa, MD2 , January 6, 2010

Over 40 million men and women in the United States have osteoporosis and low bone mineral density (BMD), placing them at risk for adverse skeletal events such as fractures and their sequelae. There are over 12 million cancer survivors in this country.

Bone Biology and the Role of the RANK Ligand Pathway
Rashmi K. Murthy, MD1, P.K. Morrow, MD2, Richard L. Theriault, MD3 , January 6, 2010

Bone renewal is essential for bone strength. During childhood and early adulthood, bone formation prevails over bone resorption, as bones increase in size and strength. Peak bone mass is achieved during the third decade in life, with a higher peak bone mass being protective against osteoporosis later in life.

Bone Disease in Multiple Myeloma
Matthew T. Drake, MD, PhD1 , January 6, 2010

Despite the significant progress that has occurred in recent decades in the treatment of many advanced malignancies, skeletal morbidity remains a major problem for patients affected by cancers that metastasize to or grow primarily within bone.

 
MEDLINE
Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis.
pubmed.gov - 2/28/13
The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences
Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer.
pubmed.gov - 2/14/13
Bone marrow-derived mesenchymal stem cells (MSCs) are reported to contribute to formation of tumor-promoting stromal cells. We reported recently that, in an orthotopic nude mice model of colon cancer, MSCs traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast (CAF)-like cells. We also found that CAFs express platelet-derived growth factor receptor (PDGFR) at a high level and that imatinib therapy targeting PDGFR in CAFs inhibits growth and metastasis of human colon cancer. These findings led us to examine whether the tumor-promoting effect of MSCs is impaired by blockade of PDGFR signaling achieved with imatinib. Orthotopic transplantation and splenic injection of human MSCs along with KM12SM human colon cancer cells, in comparison with transplantation of KM12SM cells alone, resulted in significantly greater promotion of tumor growth and liver metastasis. The KM12SM + MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell
Targeted radio-nuclide therapy of skeletal metastases.
pubmed.gov - 1/31/13
In this review, we will focus on one particular class of stromal targeted therapy, i.e. the bone seeking radiopharmaceuticals (BSRs), but will also highlight selected issues related to the bone stroma as these concepts are new, rapidly evolving, and clearly linked to the underlying BSR mechanisms of targeting and action. Herein we review clinical BSR-trials of significance with randomized trials at center stage. Furthermore, we cover a new class of BSR in late clinical development based on bone-stromal targeted alpha-particle irradiation. Lastly, we discuss potential advances in combining BSR with bisphosphonates and/or chemotherapy and emphasize the feasibility of repeated dosing.
Denosumab in patients with cancer and skeletal metastases: a systematic review and meta-analysis.
pubmed.gov - 1/31/13
We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.|A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.|Six controlled trials including 6142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80-0.88), delayed the onset of first on-study SRE (RR 0.83; 95% CI 0.75-0.90) and time to worsening of pain (RR 0.84; 95% CI 0.77-0.91). No
Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non-small-cell lung cancer patients.
pubmed.gov - 1/14/13
In the recent years, fluorine 18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) has emerged as a new modality for staging non-small-cell lung cancer (NSCLC) patients. The aim of this meta-analysis was to assess the diagnostic value of (18)F-FDG PET/CT in detecting metastatic lesions in NSCLC patients. Meta-analysis methods were used to pool sensitivity, specificity, positive and negative likehood ratios, diagnostic odd ratios and to construct a summary receiver-operating characteristic curve. Data from included studies were pooled to compare the diagnostic accuracy between PET/CT and PET or CT alone in nodal staging. Totally, 56 studies involving 8,699 patients met the inclusion criteria. The pooled sensitivities and specificities of (18)F-FDG PET/CT were 0.72 [95% confidence interval (CI): 0.65-0.78] and 0.91 (95% CI: 0.86-0.94) in determining mediastinal nodal staging; 0.71 (95% CI: 0.60-0.80) and 0.83 (95% CI: 0.77-0.88) in intrathoracic

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CLINICAL TRIALS
LAB-IMMUNOLOGY RESEARCH
neuro-oncology.oxfordjournals.org - 11/4/12
Zoledronate in Preventing Skeletal (Bone)-Related Events in Patients Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases
www.clinicaltrials.gov -
Study to Assess Efficacy and Safety of Zoledronic Acid and the Value of Markers of Bone Resorption in the Prediction of Bone Metastases and Cancer Treatment-induced Bone Loss (CTIBL) in Patients With Prostate Cancer on Hormone Therapy
www.clinicaltrials.gov -
Effect of Androgen Suppression on Bone Loss in Patients With or Without Bone Metastases Secondary to Prostate Cancer
www.clinicaltrials.gov -
Doxorubicin and Strontium-89 With or Without Celecoxib in Treating Patients With Progressive Androgen-Independent Prostate Cancer and Bone Metastases
www.clinicaltrials.gov -

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