Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate.Matsugaki A., Harada T., Kimura Y., et al. Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone. International Journal of Molecular Sciences, 19, 11, 3474. https://doi.org/10.3390/ijms19113474

Dynamic Collision Behavior Between Osteoblasts and Tumor Cells Regulates the Disordered Arrangement of Collagen Fiber/Apatite Crystals in Metastasized Bone

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate

Manganese-Enhanced MRI Reveals Early-Phase Radiation-Induced Cell Alterations In Vivo.

For tumor radiotherapy, the in vivo detection of early cellular responses is important for predicting therapeutic efficacy. Mn2+ is used as a positive contrast agent in manganese-enhanced MRI (MEMRI) and is expected to behave as a mimic of Ca2+ in many biologic systems. We conducted in vitro and in vivo MRI experiments with Mn2+ to investigate whether MEMRI can be used to detect cell alterations as an early-phase tumor response after radiotherapy. Colon-26 cells or a subcutaneously grafted colon-26 tumor model were irradiated with 20 Gy of X-rays. One day after irradiation, a significant augmentation of G2–M-phase cells, indicating a cell-cycle arrest, was observed in the irradiated cells in comparison with the control cells, although both early and late apoptotic alterations were rarely observed. The MEMRI signal in radiation-exposed tumor cells (R1: 0.77 +- 0.01 s−1) was significantly lower than that in control cells (R1: 0.82 +- 0.01 s−1) in vitro. MEMRI signal reduction was also observed in the in vivo tumor model 24 hours after irradiation (R1 of radiation: 0.97 +- 0.02 s−1, control: 1.10 +- 0.02 s−1), along with cell-cycle and proliferation alterations identified with immunostaining (cyclin D1 and Ki-67). Therefore, MEMRI after tumor radiotherapy was successfully used to detect cell alterations as an early-phase cellular response in vitro and in vivo

Best practices for multimodal clinical data management and integration: An atopic dermatitis research case

Background: In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science. Methods: We designed a generic data management flow to collect, cleanse, and integrate data to handle different types of data generated at multiple institutions by 10 types of clinical studies. We developed MeDIA (Medical Data Integration Assistant), a software to browse the data in an integrated manner and extract subsets for analysis. Results: MeDIA integrates and visualizes data and information on research participants obtained from multiple studies. It then provides a sophisticated interface that supports data management and helps data scientists retrieve the data sets they need. Furthermore, the system promotes the use of unified terms such as identifiers or sampling dates to reduce the cost of pre-processing by data analysts. We also propose best practices in clinical data management flow, which we learned from the development and implementation of MeDIA. Conclusions: The MeDIA system solves the problem of multimodal clinical data integration, from complex text data such as medical records to big data such as omics data from a large number of patients. The system and the proposed best practices can be applied not only to allergic diseases but also to other diseases to promote data-driven medical research

Brain Contrasting Ability of Blood-Brain-Barrier-Permeable Nitroxyl Contrast Agents for Magnetic Resonance RedOx Imaging

The detailed in vivo contrasting abilities of nitroxyl contrast agents in mouse brain were compared using T1-weighted MRI. Five types of five-membered-ring nitroxyl radical compound, which have been used as redox responsive contrast agents in several magnetic resonance-based imaging modalities, were tested. The blood-brain-barrier (BBB)-impermeable 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP) could not be distributed in the brain. The slightly lipophilic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP) showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic 3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MCP) had good initial uniform distribution in the brain and showed typical 2-phase signal decay profiles. A brain-seeking nitroxyl probe, acetoxymethyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl-3-carboxylate (CxP-AM), showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 4-(N-methyl piperidine)-2,2,5,5-tetramethylpyrroline-N-oxyl (23c) was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay. Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB-permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool