A simple imaging setup based on the principle of coherence-based contrast X-ray imaging with unmonochromatized synchrotron radiation was used for studying mammographic phantom and human breast specimens. The use of unmonochromatized synchrotron radiation simplifies the instrumentation, decreases the cost and makes the procedure simpler and potentially more suitable for clinical applications. The imaging systems consisted of changeable silicon wafer attenuators, a tungsten slit system, a CdWO4 scintillator screen, a CCD (Charge Coupled Device) camera coupled to optical magnification lenses, and a personal computer. In preliminary studies, a spatial resolution test pattern and glass capillary filled with air bubbles were imaged to evaluate the resOolution characteristics and coherence-based contrast enhancement. Both the spatial resolution and image quality of the proposed system were compared with those of a conventional mammography system in order to establish the characteristic advantages of this approach. The images obtained with the proposed system showed a resolution of at least 25micrometer on the test pattern with much better contrast, while the images of the capillary filled with air bubbles revealed coherence-based edge enhancement. This result shows that the coherence-based contrast imaging system, which emphasizes the refraction effect from the edge of materials of different refractive indexes, is applicable to imaging studies in fundamental medicine and biology, although further research works will be required before it can be used for clinical applications.
Breast Diseases/*radiography ; Comparative Study ; Female ; Humans ; Mammography/*instrumentation/*methods ; *Phantoms, Imaging ; Pilot Projects ; Research Support, Non-U.S. Gov't ; *Synchrotrons ; X-Rays

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Ionizing radiation has long been used in medicine since the discovery of X-rays. Diagnostic imaging using synchrotron radiation has been under investigation since Rubenstein et al. reported dual-energy iodine-K-edge subtraction coronary angiography. Recently, computed tomography (CT) and magnetic resonance imaging (MRI) have provided better quality results than conventional radiology, providing important information on human internal structures. However, such techniques are unable to detect fine micron sized structures for the early diagnosis of tumors, vascular diseases and other medical objectives. Third generation synchrotron X-rays are well known for their superiority in coherence and energy tunability with respect to conventional X-rays. Consequently, new contrast mechanisms with a superior spatial resolution are becoming available. Here we present the extremely fine details of live animal internal structures using unmonochromatized synchrotron X-rays (white beam) and a simple detector system. Natural movements of the internal organs are also shown. The results indicate that this imaging technique can be applied to investigating microstructures and evaluating the function of the internal organs. Furthermore, this imaging system may be applied to humans as the next tool beyond CT and MRI.
Animal ; *Diagnostic Imaging ; Male ; Mice ; Mice, Inbred HRS ; *Synchrotrons

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.
Adult ; Allopurinol ; Anaphylaxis ; Anti-Bacterial Agents ; Asia ; Asian Continental Ancestry Group ; Aspirin ; Asthma ; Carbamazepine ; Child ; Cicatrix ; Contrast Media ; Coronary Artery Disease ; Diagnostic Tests, Routine ; Drug Hypersensitivity ; Ethnic Groups ; Humans ; Hypersensitivity ; Penicillins ; Percutaneous Coronary Intervention ; Phenotype ; Recurrence ; Skin Tests