Interleukin-6 receptor inhibitor suppresses bone metastases in a breast cancer cell line

Abstract

Background

Interleukin-6 (IL-6) is a potent inflammatory cytokine that appears to play a key role in cancer growth and metastasis. In the present study, the effects of IL-6 receptor (IL-6R) on breast cancer aggressiveness and bone metastases were investigated.

Methods

MDA-MB-231 (MDA-231) cells were treated in the presence or absence of anti-human IL-6 receptor (IL-6R) monoclonal antibody and examined with respect to cell survival. The expressions of signal transducer and activator of transcription 3 (Stat3), vascular endothelial growth factor (VEGF), and receptor activator of NF-κB (RANK) were analyzed by SDS-PAGE and immunoblotting. MDA-231 cells were injected into the left ventricle of mice, and then anti-human IL-6R monoclonal antibody or saline was administered intraperitoneally for 28 days. After 28 days, the incidence of bone metastases was evaluated in the hind limbs by radiography and histology.

Results

Anti-human IL-6R monoclonal antibody reduced bone metastases in an animal model injected with MDA-231 cells on radiological and histomorphometric analyses. The mechanism of bone metastasis inhibition involved inhibited cell proliferation and decreased expressions of phospho-Stat3, VEGF, and RANK in MDA-231 cells.

Conclusions

The results of the present study suggest that inhibition of IL-6 signaling may become a preventive therapeutic option for breast cancer and bone metastases.

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Cancers, Vol. 10, Pages 80: Aptamer Therapeutics in Cancer: Current and Future

Cancers, Vol. 10, Pages 80: Aptamer Therapeutics in Cancer: Current and Future

Cancers doi: 10.3390/cancers10030080

Authors: Yoshihiro Morita Macall Leslie Hiroyasu Kameyama David Volk Takemi Tanaka

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small—approximately one-tenth that of monoclonal antibodies—their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers' long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen® (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.

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Cancers, Vol. 10, Pages 80: Aptamer Therapeutics in Cancer: Current and Future

Cancers, Vol. 10, Pages 80: Aptamer Therapeutics in Cancer: Current and Future

Cancers doi: 10.3390/cancers10030080

Authors: Yoshihiro Morita Macall Leslie Hiroyasu Kameyama David Volk Takemi Tanaka

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small—approximately one-tenth that of monoclonal antibodies—their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers' long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen® (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.

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From imaging to reimbursement: what the pediatric radiologist needs to know about health care payers, documentation, coding and billing

Abstract

Medical coding and billing processes in the United States are complex, cumbersome and poorly understood by radiologists. Despite the direct implications of radiology documentation on reimbursement, trainees and practicing radiologists typically receive limited relevant training. This article summarizes the payer structure including the state-based Children's Health Insurance Programs, discusses the essential processes by which radiologists request and receive reimbursement, details the mechanisms of coding diagnoses using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and imaging services using Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes, and explores reimbursement and coding-related issues specific to pediatric radiology. Appropriate documentation, informed by knowledge of coding, billing and reimbursement fundamentals, facilitates appropriate payment for clinically relevant services provided by pediatric radiologists.

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From imaging to reimbursement: what the pediatric radiologist needs to know about health care payers, documentation, coding and billing

Abstract

Medical coding and billing processes in the United States are complex, cumbersome and poorly understood by radiologists. Despite the direct implications of radiology documentation on reimbursement, trainees and practicing radiologists typically receive limited relevant training. This article summarizes the payer structure including the state-based Children's Health Insurance Programs, discusses the essential processes by which radiologists request and receive reimbursement, details the mechanisms of coding diagnoses using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and imaging services using Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes, and explores reimbursement and coding-related issues specific to pediatric radiology. Appropriate documentation, informed by knowledge of coding, billing and reimbursement fundamentals, facilitates appropriate payment for clinically relevant services provided by pediatric radiologists.

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Aortic stent graft injury over active blood flow: over the fence

Description

A 72-year-old woman was admitted to our hospital complaining of chest pain at rest. She underwent thoracic endovascular repair (TER) using three stent grafts (GORE TAG 34x150, 34x200 and 26x200 mm; W. L. Gore & Associates, Flagstaff, Arizona, USA) with type B aortic dissection 5 years earlier (figure 1A). Coronary CT angiography (CTA) findings were inconclusive because of remarkable massive calcification in all coronary arteries. As a low-density area suspected of mural thrombus inside the second stent graft was detected (figure 1B), non-obstructive angioscopy was performed to evaluate graft failure besides invasive coronary angiography.1 No significant stenosis was found using invasive coronary angiography; however, suspicious blood flow through the graft was observed at the aneurysmal descending aorta in the middle of the second graft (figure 2 and video 1). Being uninfluenced by aortic blood flow, it was thought to exist...

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A shift from papillary to reticular fibroblasts enables tumour–stroma interaction and invasion

A shift from papillary to reticular fibroblasts enables tumour–stroma interaction and invasion

A shift from papillary to reticular fibroblasts enables tumour–stroma interaction and invasion, Published online: 19 March 2018; doi:10.1038/s41416-018-0024-y

A shift from papillary to reticular fibroblasts enables tumour–stroma interaction and invasion

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