ABSTRACT
BACKGROUND: The bone represents one of the most common sites of metastases in breast cancer. The aim of the current study was to evaluate the diagnostic potential of several circulating markers to detect metastasis to bones in patients with breast cancer. PATIENTS AND METHODS: Receptor activator of Nuclear Factor-kappa ß (NF-Kß) ligand (RANKL), osteoprotegrin (OPG), vitamin D (VIT D), Chitinase-3-like protein 1; also known as YKL-40, topoisomerase IIα (TOPO2a), and human epidermal growth factor receptor 2 (HER2) were measured in blood samples obtained from 122 patients with breast cancer and 25 healthy controls. RESULTS: All biomarkers were significantly elevated in patients with breast cancer with bone metastasis compared with nonmetastatic patients except YKL-40. RANKL had the highest diagnostic performance for bone metastasis detection with an area under the curve of 97.3, a sensitivity of 85%, and a specificity of 98.6%. Furthermore, logistic regression analysis resulted in a model of RANKL combined with HER2 that had even higher discriminatory power of metastasis to bones than that of RANKL alone. Overall correct classification of the model was 98.9%. CONCLUSION: We recommend that measuring RANKL together with HER2 can be routinely applied to allow early detection of bone metastases in patients with breast cancer.
Subject(s)
Biomarkers, Tumor/blood , Bone Neoplasms/diagnosis , Breast Neoplasms/pathology , Early Detection of Cancer/methods , RANK Ligand/blood , Receptor, ErbB-2/blood , Adult , Biopsy , Bone Neoplasms/blood , Bone Neoplasms/secondary , Breast/diagnostic imaging , Breast/pathology , Breast Neoplasms/blood , Breast Neoplasms/diagnostic imaging , Chitinase-3-Like Protein 1/blood , DNA Topoisomerases, Type II/blood , Female , Humans , Logistic Models , Mammography , Osteoprotegerin/blood , Poly-ADP-Ribose Binding Proteins/blood , Vitamin D/bloodABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX. MATERIALS AND METHODS: The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis. RESULTS: The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1ß, prostaglandin E2, nuclear factor-κß, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α. CONCLUSION: LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.
Subject(s)
Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Micelles , Nanoparticles/chemistry , Piroxicam/analogs & derivatives , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arthritis, Experimental/blood , Arthritis, Experimental/complications , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/pathology , Biomarkers/blood , Carrageenan , Chronic Disease , Dinoprostone/blood , Disease Models, Animal , Edema/blood , Edema/complications , Edema/drug therapy , Edema/pathology , Freund's Adjuvant , Interleukin-1beta/blood , Male , Nanoparticles/ultrastructure , Piroxicam/pharmacology , Piroxicam/therapeutic use , Polymers/chemistry , Rats, Wistar , Thiobarbituric Acid Reactive Substances/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor-initiating, metastatic, and drug resistance properties. This study was conducted to evaluate the effects of PEGylated interferon-α2a (PEG-IFN-α2a) and 5-fluorouracil (5-FU) on the expression of CSC markers and on specific pathways that contribute to the propagation of CSCs in HCC. HCC was initiated in rats using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for 6 weeks. After the appearance of dysplastic nodules, the animals received PEG-IFN-α2a or 5-FU for 8 weeks. CSC markers (OV6, CD90) and molecules related to transforming growth factor ß (TGF-ß) and other signaling pathways were assessed in hepatic tissues. The PEG-IFN-α2a treatment effectively suppressed the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic expression of TGF-ß receptor II (TGF-ßRII) and ß2-spectrin (ß2SP), and significantly reduced the elevated hepatic expression of TGF-ß1, interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3), and vascular endothelial growth factor (VEGF). In contrast, the 5-FU treatment failed to reduce the overexpression of CSC markers and barely affected the disrupted TGF-ß signaling. Furthermore, it had no effect on angiogenesis or nitrosative stress. PEG-IFN-α2a, but not 5-FU, could reduce the propagation of CSCs during the progression of HCC by upregulating the disrupted TGF-ß signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis.
