Assessment of Renal Osteodystrophy via Computational Analysis of Label-free Raman Detection of Multiple Biomarkers.

Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is through a fast, label-free Raman recording of multiple biomarkers combined with computational analysis for predicting the minimally required number of spectra for sample classification at defined accuracies. Four clinically relevant biomarkers: the mineral-to-matrix ratio, the carbonate-to-matrix ratio, phenylalanine, and calcium contents were experimentally determined and simultaneously considered as input to a linear discriminant analysis (LDA).

STIM1 expression is associated with osteosarcoma cell survival.

Objective: To examine the role of store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca contributes to the regulation of osteosarcoma cells.

Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation.

Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells.

Background: Osteosarcoma is the most common bone cancer. Despite advances, molecular mechanisms associated with osteosarcoma have not been fully understood. Hence, an effective treatment for osteosarcoma has yet to be developed.

Decreased local and systemic levels of sFRP3 protein in osteosarcoma patients.

Osteosarcoma is a malignant bone tumor that occurs mainly in children and adolescents. Because Wnt signaling has been implicated in the pathogenesis of osteosarcoma, we have investigated the circulating and local levels of the Wnt antagonist protein, Secreted Frizzled Related Protein (sFRP) 3, in osteosarcoma patients. Enzyme linked immunosorbent assay (ELISA) analysis of 67 osteosarcoma and age-matched non-diseased control sera showed that sFPR3 protein levels were significantly lower in osteosarcoma than in normal.

Raman Spectroscopic and Microscopic Analysis for Monitoring Renal Osteodystrophy Signatures.

Defining the pathogenesis of renal osteodystrophy (ROD) and its treatment efficacy are difficult, since many factors potentially affect bone quality. In this study, confocal Raman microscopy and parallel statistical analysis were used to identify differences in bone composition between healthy and ROD bone tissues through direct visualization of three main compositional parametric ratios, namely, calcium content, mineral-to-matrix, and carbonate-to-matrix. Besides the substantially lower values found in ROD specimens for these representative ratios, an obvious accumulation of phenylalanine is Raman spectroscopically observed for the first time in ROD samples and reported here.

Efflux inhibition by IWR-1-endo confers sensitivity to doxorubicin effects in osteosarcoma cells.

Osteosarcoma is the most common bone tumor that affects children and young adults. Despite advances in the use of combination chemotherapy regimens, response to neoadjuvant chemotherapy in osteosarcoma remains a key determinant of patient outcome. Recently, highly potent small molecule inhibitors of canonical Wnt signaling through the poly(ADP-ribose) polymerase (PARP)-family enzymes, tankyrases 1 & 2 (Tnks1/2), have been considered as possible chemotherapy sensitizing agents.

Olaratumab for the treatment of advanced soft tissue sarcoma.

Olaratumab, a human monoclonal antibody against platelet derived growth factor receptor alpha (PDGFR- α), is the first drug that in combination with doxorubicin for the treatment of patients with advanced/metastatic soft tissue sarcoma (STS) that has showed an improved overall survival compared to doxorubicin alone. These initial results are exciting and have the potential to change the landscape of treatment for patients with STS. Areas covered: This article reviews the development of olaratumab for oncology use by reviewing articles in PubMed for 'platelet derived growth factor' and 'receptor' and 'soft tissue sarcoma'.

FH535 Suppresses Osteosarcoma Growth and Inhibits Wnt Signaling through Tankyrases.

Osteosarcoma (OS) is an aggressive primary bone tumor which exhibits aberrantly activated Wnt signaling. The canonical Wnt signaling cascade has been shown to drive cancer progression and metastasis through the activation of β-catenin. Hence, small molecule inhibitors of Wnt targets are being explored as primary or adjuvant chemotherapy.

Inhibiting DNA-PK radiosensitizes human osteosarcoma cells.

Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK), is an attractive option for the radiosensitization of osteosarcoma.

Invertible micellar polymer nanoassemblies target bone tumor cells but not normal osteoblast cells.

Aim: To demonstrate the capability of the invertible micellar polymer nanoassemblies (IMAs) to deliver and release curcumin using the recently discovered mechanism of macromolecular inversion to treat bone tumor cells.

Materials & Methods: The effect of IMA-mediated delivery of curcumin on osteosarcoma cell survival was investigated using MTS assays. To assess the effect of IMAs-delivered curcumin on osteosarcoma cell growth, fluorescence-activated cell sorting was performed.

2-Methoxyestradiol-Mediated Induction of Frzb Contributes to Cell Death and Autophagy in MG63 Osteosarcoma Cells.

Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells.

Molecular strategies for modulating Wnt signaling.

The importance of the Wnt signaling cascade in the fields of developmental biology, regenerative medicine, cancer genetics, and neurobiology has fueled a wide search for potent pharmacological agents capable of controlling Wnt signaling. Numerous fields of study have lent assistance to this endeavor, yielding both natural and synthetic compounds that are capable of inducing or inhibiting Wnt at multiple stages within the pathway. Further, there is a large of body research which has investigated endogenous Wnt inducers and inhibitors, namely the secreted Wnts, Dickkof proteins, secreted Frizzled-Related Proteins, and Wnt Inhibitory Factor-1, along with others which may act via indirect means to stimulate or inhibit Wnt (e.

Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin's therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles) as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

The estrogen metabolite 2-methoxyestradiol regulates eukaryotic initiation factor 4E (eIF4E) and inhibits protein synthesis in MG63 osteosarcoma cells.

Osteosarcoma is a primary bone tumor that affects children and young adults. The estrogen metabolite 2-methoxyestradiol (2-ME) induces cell death in osteosarcoma cells. To determine whether 2-ME actions involve the control of protein synthesis, we studied the effect of 2-ME on eukaryotic initiation factor 4E (eIF4E) and eIF4E-binding protein 1 (4E-BP1) in MG63 osteosarcoma cells.

Inhibition of Autophagy Increases 2-Methoxyestradiol-Induced Cytotoxicity in SW1353 Chondrosarcoma Cells.

Chondrosarcoma is a cartilage tumor and is the second most common malignant bone cancer. Unlike many tumors, chondrosarcomas are resistant to conventional chemotherapy and radiotherapy. Autophagy is a homeostatic mechanism through which cellular proteins and organelles are subjected to lysosomal degradation and recycling.

Tissue engineered constructs: perspectives on clinical translation.

In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions.

MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.

Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated.

RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells.

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Surgical resection and adjunctive chemotherapy are the only widely available options of treatment for this disease. Anti-tumor compound 2-Methoxyestradiol (2-ME) triggers cell death through the induction of apoptosis in osteosarcoma cells, but not in normal osteoblasts.

Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival.

Fusion of dynactin 1 to anaplastic lymphoma kinase in inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor is an uncommon neoplasm that occurs more often in younger patients. Approximately 50% of inflammatory myofibroblastic tumors are characterized by anaplastic lymphoma kinase fusion genes, more commonly TPM3-anaplastic lymphoma kinase and TPM4-anaplastic lymphoma kinase. Herein, we report a novel fusion of dynactin 1 to anaplastic lymphoma kinase in a neck inflammatory myofibroblastic tumor diagnosed in a 7-year-old girl.

Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells.

Background: Osteosarcoma is a bone tumor that often affects children and young adults. Although a combination of surgery and chemotherapy has improved the survival rate in the past decades, local recurrence and metastases still develop in 40% of patients. A definite therapy is yet to be determined for osteosarcoma.

High-resolution genomic mapping reveals consistent amplification of the fibroblast growth factor receptor substrate 2 gene in well-differentiated and dedifferentiated liposarcoma.

Well-differentiated liposarcoma (WDLS) is one of the most common malignant mesenchymal tumors and dedifferentiated liposarcoma (DDLS) is a malignant tumor consisting of both WDLS and a transformed nonlipogenic sarcomatous component. Cytogenetically, WDLS is characterized by the presence of ring or giant rod chromosomes containing several amplified genes, including MDM2, TSPAN31, CDK4, and others mainly derived from chromosome bands 12q13-15. However, the 12q13-15 amplicon is large and discontinuous.