Recent Advances in Bioimaging for Cancer Research

Molecular imaging techniques as well as nanoparticle applicable to molecular imaging are being explored to improve the cancer detection accuracy, which help to manage efficiently at the early stage. Among the various imaging technologies, optical imaging is a highly sensitive detection technique that allows direct observation of specific molecular events, biological pathways, and disease processes in real time through imaging probes that emit light in a range of wavelengths. Recently, nanoparticles have provided significant progresses that can be simultaneously used for cancer diagnosis and therapy (cancer theranostics). Theranostics aims to provide “image-guided cancer therapy,” by integrating therapeutic and imaging agents in a single platform. In addition, molecular imaging techniques facilitate “image-guided surgery” enabling maximization of tumor excision and minimization of side effects. The optical signals generated by fluorescence nanoparticles offer the possibility to distinguish tumor sites and normal tissues during surgery by real-time guidance, thereby increasing the long-term patient survival. These techniques will considerably contribute to reducing cancer recurrence and developing more effective cures. In this chapter, we will introduce diverse research on nanomaterials-based optical imaging for effective cancer therapy

Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from mitochondria to the ER in cancer cells

Background: Resistance to cell death in the presence of stressful stimuli is one of the hallmarks of cancer cells acquired during multistep tumorigenesis, and knowledge of the molecular mechanism of stress adaptation can be exploited to develop cancer-selective therapeutics. Mitochondria and the endoplasmic reticulum (ER) are physically interconnected organelles that can sense and exchange various stress signals. Although there have been many studies on stress propagation from the ER to mitochondria, reverse stress signals originating from mitochondria have not been well reported.Methods: After inactivation of the proteins by pharmacologic and genetic methods, the signal pathways were analyzed by fluorescence microscopy, flow cytometry, MTT assay, and western blotting. A mouse xenograft model was used to examine synergistic anticancer activity and the action mechanism of drugs in vivo.Results: We show in this study that mitochondrial heat shock protein 90 (Hsp90) suppresses mitochondria-initiated calcium-mediated stress signals propagating into the ER in cancer cells. Mitochondrial Hsp90 inhibition triggers the calcium signal by opening the mitochondrial permeability transition pore and, in turn, the ER ryanodine receptor, via calcium-induced calcium release. Subsequent depletion of ER calcium activates unfolded protein responses in the ER lumen, thereby increasing the expression of a pro-apoptotic transcription factor, CEBP homologous protein (CHOP). Combined treatment with the ER stressor thapsigargin and the mitochondrial Hsp90 inhibitor gamitrinib augmented interorganelle stress signaling by elevating CHOP expression, and showed synergistic cytotoxic activity exclusively in cancer cells in vitro and in vivo.Conclusions: Collectively, mitochondrial Hsp90s confer cell death resistance to cancer cells by suppressing the mitochondria-initiated calcium-mediated interorganelle stress response.open0

Chirality of Intermediate Filaments and Magnetic Helicity of Active Regions

Filaments which form either between or around active regions (ARs) are called intermediate filaments. In spite of various theoretical studies, the origin of the chirality of filaments is still uncovered. We investigated how intermediate filaments are related to their associated ARs, especially from the point of view of magnetic helicity and the orientation of polarity inversion lines (PILs). The chirality of filaments has been determined based on the orientations of barbs observed in BBSO full-disk Halpha images taken during the rising phase of solar cycle 23. The sign of magnetic helicity of ARs has been determined using S/inverse-S shaped sigmoids from Yohkoh SXT images. As a result, we have found a good correlation between the chirality of filaments and the magnetic helicity sign of ARs. Among 45 filaments, 42 filaments have shown the same sign as helicity sign of nearby ARs. It has been also confirmed that the role of both the orientation and the relative direction of PILs to ARs in determining the chirality of filaments is not significant, against a theoretical prediction. These results suggest that the chirality of intermediate filaments may originate from magnetic helicity of their associated ARs.Comment: 13 pages, 7 figures, Accepted for Ap