Comparison of 3-month cytogenetic and molecular assays for early assessment of long-term clinical impact after BCR-ABL1 tyrosine kinase inhibitor treatment in chronic myeloid leukemia.

To compare the clinical significance of 3-month cytogenetic and molecular monitoring, we analyzed 1,410 paired cytogenetic and molecular data from 705 chronic-phase chronic myeloid leukemia patients. Based on early cytogenetic response (ECyR, Ph+≤35 %) and molecular response (EMR, BCR-ABL1IS≤10 %) at 3 months, the patients were divided into four groups (group 1: ECyR + EMR, n = 560; group 2: no ECyR + EMR, n = 27; group 3: ECyR + no EMR, n = 55; group 4: no ECyR + no EMR, n = 63). By 10 years, major molecular response (MMR), deep molecular response (MR4.5), overall survival (OS), and progression-free survival (PFS) rates were significantly high in group 1 (P < 0.001). Comparing groups 2 and 3, the MMR (P = 0.096), MR4.5 (P = 0.945), OS (P = 0.832), and PFS (P = 0.627) rates tended to be higher in group 2, although not significantly. Thus, the cytogenetic assay can not only be useful but its addition may also provide a more precise prediction of MR4.5.

Topography and Anatomical Variations of the Axillary Artery.

Knowledge of anatomical variations of the limb's main arteries is significant for the clinicians. Thus, this study is aimed at examining the branching pattern and anatomical variations of the axillary artery. We conducted research on 59 upper limbs of adult human donated cadavers. All axillary artery branches' origins were assessed, and the correlations between points of origins and variations of specific branches were evaluated. The average length of the axillary artery was found to be 11.22 cm, and this length was defined as reference line. Based on this reference line, the first, second, and third parts were 37.56%, 39%, and 30.05%, respectively. The STA was originated from 25.11%. The TAA and LTA were 42.67% and 54.82%, respectively. The SSA, ACHA, and PCHA were 64.72%, 83.89%, and 84.53%, respectively. The origin of LTA was correlated with that of SSA (R = 0.473, P < 0.05) and AHCA (R = 0.307, P < 0.05), respectively. And there was a positive correlation between AHCA and PHCA (R = 0.705, P < 0.05). The number of branches ranged from 3~6, and 9 types were shown. The most frequent branching pattern was common origin of the LTA and SSA (22/59). And AHCA and PHCA were originated together in 19 cases, and both patterns were combined in 12 cases. TTA and LTA branched together in 9 cases, and common trunk for the SSA, PHCA, and AHCA was found in 2 cases. According to this pattern, the origin of LTA and PCHA was significantly different. This information is particularly useful for surgeons and clinicians.

Enhanced Energy Efficiency of Light Grid System with Optimized System Design and Recycling with Thermoelectric Platform.

In this work, a light grid system with a high-power LED chip was manufactured and employed to analyze the energy efficiency of output optical energy. The high-power LED system based on thermoelectric modules, a heat dissipation structure and optical transmission system with an optical fiber were optimally combined and designed, which increased the efficiency of light grid system. Additionally, by introducing an effective design for the heat dissipation structure, the output optical energy and recycled electrical energy were increased. The recycled energy through optimized heat dissipation structure was 1.94 W, and the system efficiency of designed light grid system is more than 50%. In this research, we intensively studied the energy efficiency of a light grid system as well as the recycling of thermal energy through thermoelectric modules.

Improved Multilayered (Bi,Sc)O3-(Pb,Ti)O3 Piezoelectric Energy Harvesters Based on Impedance Matching Technique.

As a piezoelectric material, (Bi,Sc)O3-(Pb,Ti)O3 ceramics have been tested and analyzed for sensors and energy harvester applications owing to their relatively high Curie temperature and high piezoelectric coefficient. In this work, we prepared optimized (Bi,Sc)O3-(Pb,Ti)O3 piezoelectric materials through the conventional ceramic process. To increase the output energy, a multilayered structure was proposed and designed, and to obtain the maximum output energy, impedance matching techniques were considered and tested. By varying and measuring the energy harvesting system, we confirmed that the output energies were optimized by varying the load resistance. As the load resistance increased, the output voltage became saturated. Then, we calculated the optimized output power using the electric energy formula. Consequently, we identified the highest output energy of 5.93 µW/cm2 at 3 MΩ for the quadruple-layer harvester and load resistor using the impedance matching system. We characterized and improved the electrical properties of the piezoelectric energy harvesters by introducing impedance matching and performing the modeling of the energy harvesting component. Modeling was conducted for the piezoelectric generator component by introducing the mechanical force dependent voltage sources and load resistors and piezoelectric capacitor connected in parallel. Moreover, the generated output voltages were simulated by introducing an impedance matching technique. This work is designed to explain the modeling of piezoelectric energy harvesters. In this model, the relationship between applied mechanical force and output energy was discussed by employing experimental results and simulation.

Synchrotron tomographic images from human lung adenocarcinoma: Three-dimensional reconstruction and histologic correlations.

High-resolution tomographic images using synchrotron X-rays are expected to provide detailed reflection of microstructures, thereby allowing for the examination of histologic structures without destruction of the specimen. This study aims to evaluate the synchrotron tomographic images of mixed ground-glass opacity excised on 5-mm sections in comparison to pathologic examination. The Institutional Review Board of our institute approved this retrospective study, and written informed consent was obtained from each patient whose lung tissue would be used. Obtained lung cancer specimens were brought to the multiple Wiggler 6C beam line at the Pohang Light Source (PLS-II) in Korea, and phase contrast X-ray images were obtained in November 2016. The X-ray emanated from a bending magnet of the electron storage ring with electron energy of 3 GeV, and a typical beam current was 320 mA. Reconstructed tomographic images were compared with images from histologic slides obtained from the same samples. Pulmonary microstructures including terminal bronchioles, alveolar sacs, and vasculature were identified with phase contrast X-ray images. Images from normal lung tissue and mixed ground-glass opacity were clearly distinguishable. Hyperplasia of the interalveolar septum and dysplasia of microstructure were clearly identified. The imaging findings correlated well with hematoxylin-eosin stained specimens. Tomographic images using synchrotron radiation have the potential for clinical applications. With refinement, this technique may become a diagnostic tool for detection of lung cancer.

Tracheal compression by aberrant brachiocephalic trunk accompanying variant origin of the vertebral artery / Compresión traqueal por un tronco braquiocefálico aberrante acompañado de una variación en el origen de la arteria vertebral

The aorta is the main arterial trunk in the human body, however, its variation was extremely variable. During an educational dissection, aberrant branching pattern of aortic arch was found in a Korean cadaver. The brachiocephalic trunk (innominate artery) originated from the aortic arch at the left side of the trachea. It crossed the trachea and divided into the right common carotid and subclavian arteries. The left vertebral artery originated from the aortic arch between the origins of the left common carotid artery and the left subclavian artery, then the left vertebral artery coursed upward to the transverse foramen of the C7. The author describes this previously novel case report with aberrant brachiocephalic trunk and left vertebral arteries and discusses the clinical implications of such a variant.

La aorta es el tronco arterial principal del cuerpo humano, sin embargo, su variación es extremadamente variable. Durante una disección de rutina de un cadáver coreano, se encontró un patrón de ramificación aberrante del arco aórtico. El tronco braquiocefálico se originaba del arco aórtico en el lado izquierdo de la tráquea. Cruzaba la tráquea y se dividía en las arterias carótida común y subclavia derecha. La arteria vertebral izquierda se originó a partir del arco aórtico entre los orígenes de la arteria carótida común izquierda y la arteria subclavia izquierda, luego la arteria vertebral izquierda ascendió hacia el foramen transversal de la séptima vértebra cervical. Se describe un caso de tronco braquiocefálico aberrante y la correspondiente arteria vertebral izquierda y se discuten las implicaciones clínicas de tal variante.

Effects of pH, dissolved organic matter, and salinity on ibuprofen sorption on sediment.

Ibuprofen is well known as one of the most frequently detected pharmaceuticals and personal care products (PPCPs) in rivers. However, sorption of ibuprofen onto sediment has not been considered in spite of its high K ow (3.5). In this study, the effects of various environmental conditions such as pH (4, 5.3, and 7), the concentrations of dissolved organic matters (0 to 1.0 mM citrate and urea), salinity (0, 10, 20, and 30 part per thousand), and presence of other PPCP (salicylic acid) on ibuprofen sorption were investigated. Linear model mainly fitted the experimental data for analysis. The distribution coefficient (K d) in the linear model decreased from 6.76 at pH 4 to near zero at pH 7, indicating that neutral form of ibuprofen at pH below pKa (5.2) was easily sorbed onto the sediment whereas the sorption of anionic form at pH over pKa was not favorable. To investigate the effect of dissolved organic matters (DOMs) on ibuprofen sorption, citrate and urea were used as DOMs. As citrate concentration increased, the K d value decreased but urea did not interrupt the ibuprofen sorption. Citrate has three carboxyl functional groups which can attach easily ibuprofen and hinder its sorption onto sediment. Salinity also affected ibuprofen sorption due to decrease of the solubility of ibuprofen as salinity increased. In competitive sorption experiment, the addition of salicylic acid also led to enhance ibuprofen sorption. Conclusively, ibuprofen can be more easily sorbed onto the acidified sediments of river downstream, especially estuaries or near-shore environment with low DOM concentration.

Synchrotron nanoscopy imaging study of scalp hair in breast cancer patients and healthy individuals: Difference in medulla loss and cortical membrane enhancements.

Nanoscopic synchrotron X-ray imaging was performed on scalp hair samples of patients with breast cancer and healthy individuals to investigate any structural differences as diagnostic tool. Hair strands were divided into 2-3 segments along the strands from root to tip, followed by imaging either in projection or in CT scanning with a monochromatic 6.78-keV X-ray using zone-plate optics with a resolving power of 60 nm. All the examined cancer hairs exhibited medulla loss with cancer stage-dependent pattern; complete loss, discontinuous or trace along the strands. In contrast, medullas were well retained without complete loss in the healthy hair. In the CT-scanned axial images, the cortical spindle compartments had no contrast in the healthy hair, but appeared hypointense in contrast to the surrounding hyperintense cortical membrane complex in the cancer hair. In conclusion, observation of medulla loss and cortical membrane enhancements in the hair strands of breast cancer patients demonstrated structural variations in the cancer hair, providing a new platform for further synchrotron X-ray imaging study of screening breast cancer patients.

A radial artery originating from the thoracoacromial artery.

PURPOSE: The purpose of this case report is to report a rare vascular variation in the upper limbs because of its clinical importance and embryological implication. METHODS: During the educational dissection of a 73-year-old Korean male cadaver`s right upper limb, we found a variant branch which is originated from the thoracoacromial artery. RESULTS: The variant branch from the thoracoacromial artery ran to the distal forearm in the deep fascia. Because it finally coursed like the radial artery in the forearm and the palm, we defined the variant artery as superficial brachioradial artery (SBRA). In the cubital region a little below the intercondylar line, the brachial artery gave off a small communicating branch to SBRA, and continued as the ulnar artery. CONCLUSIONS: We reported this unique variation and discussed its clinical and embryological implication.

Pin1 promotes neuronal death in stroke by stabilizing Notch intracellular domain.

OBJECTIVE: Stroke is a leading cause of mortality and disability. The peptidyl-prolyl cis/trans isomerase Pin1 regulates factors involved in cell growth. Recent evidence has shown that Pin1 plays a major role in apoptosis. However, the role of Pin1 in ischemic stroke remains to be investigated. METHODS: We used Pin1 overexpression and knockdown to manipulate Pin1 expression and explore the effects of Pin1 in cell death on ischemic stress in vitro and in a mouse stroke model. We also used Pin 1 inhibitor, γ-secretase inhibitor, Notch1 intracellular domain (NICD1)-deleted mutant cells, and Pin1 mutant cells to investigate the underlying mechanisms of Pin1-NICD1-mediated cell death. RESULTS: Our findings indicate that Pin1 facilitates NICD1 stability and its proapoptotic function following ischemic stroke. Thus, overexpression of Pin1 increased NICD1 levels and enhanced its potentiation of neuronal death in simulated ischemia. By contrast, depletion or knockout of Pin1 reduced the NICD1 level, which in turn desensitized neurons to ischemic conditions. Pin1 interacted with NICD1 and increased its stability by inhibiting FBW7-induced polyubiquitination. We also demonstrate that Pin1 and NICD1 levels increase following stroke. Pin1 heterozygous (+/-) and knockout (-/-) mice, and also wild-type mice treated with an inhibitor of Pin1, each showed reduced brain damage and improved functional outcomes in a model of focal ischemic stroke. INTERPRETATION: These results suggest that Pin1 contributes to the pathogenesis of ischemic stroke by promoting Notch signaling, and that inhibition of Pin1 is a novel approach for treating ischemic stroke.

Propagation-based phase-contrast X-ray microtomography of a cerebral protection device retrieved after carotid artery stenting.

Phase-contrast synchrotron X-ray microtomography (pcSyncX) based on the highly coherent X-ray beam has previously been used to visualize the microstructures of biologic specimens, but it has never been used to evaluate embolic debris adherent on a cerebral protection device (CPD). The purpose of this study was to demonstrate the feasibility of pcSyncX for evaluating embolic debris during carotid artery stenting (CAS). Five patients (four males, age range 67-77 years) with severe carotid artery stenosis underwent CAS. The retrieved CPD was exposed to synchrotron radiation and 1000 pcSyncX projection images were obtained by rotating the CPD through 180°. An X-ray shadow of a CPD was converted into a visual image by the scintillator. After microtomographic reconstruction, the three-dimensionally reconstructed images were further segmented into the embolic debris and CPD. The total volume of emboli was calculated by summing the volume at each scanning level. The number of membrane pores covered by emboli as seen from the outer surface was counted and the percentage of covered area was calculated. Embolic debris was clearly demonstrated not only on the inner surface and within pores but also on the outer surface of the CPD. The mean total volume of embolic debris was 0.538 × 10(-6) mm(3) (range 0.225-0.965 × 10(-6) mm(3)). Most (61.5%) of the debris was located at the apical one-third of the CPD and 20.8% of the pore area was covered by debris.

Correlative microscopy methods that maximize specimen fidelity and data completeness, and improve molecular localization capabilities.

Correlative microscopy techniques interrogate biological systems more thoroughly than is possible using a single modality. This is particularly true if disparate data types can be acquired from the same specimen. Recently, there has been significant progress towards combining the structural information obtained from soft X-ray tomography (SXT) with molecular localization data. Here we will compare methods for determining the position of molecules in a cell viewed by SXT, including direct visualization using electron dense labels, and by indirect methods, such as fluorescence microscopy and high numerical aperture cryo-light microscopy. We will also discuss available options for preserving the in vivo structure and organization of the specimen during multi-modal data collection, and how some simple specimen mounting concepts can ensure maximal data completeness in correlative imaging experiments.

Large-field high-contrast hard x-ray Zernike phase-contrast nano-imaging beamline at Pohang Light Source.

We developed an off-axis-illuminated zone-plate-based hard x-ray Zernike phase-contrast microscope beamline at Pohang Light Source. Owing to condenser optics-free and off-axis illumination, a large field of view was achieved. The pinhole-type Zernike phase plate affords high-contrast images of a cell with minimal artifacts such as the shade-off and halo effects. The setup, including the optics and the alignment, is simple and easy, and allows faster and easier imaging of large bio-samples.

Enhanced proton treatment in mouse tumors through proton irradiated nanoradiator effects on metallic nanoparticles.

The impact of protons on metallic nanoparticles (MNPs) produces the potent release of MNP-induced secondary electrons and characteristic x-rays. To determine the ability of secondary radiations to enhance proton treatment, the therapeutic irradiation of tumors was investigated in mice receiving 100-300 mg MNPs/kg intravenously prior to single dose, 10-41 Gy, proton irradiation. A proton beam was utilized to irradiate nanoparticles with a single Bragg peak set to occur inside a tumor volume (fully absorbed) or to occur after the beam had traversed the entire body. The dose-dependent increase in complete tumor regression (CTR) was 37-62% in the fully-absorbed irradiation group or 50-100% in the traversing irradiation group, respectively, compared with the proton-alone control mice (p < 0.01). One year survival was 58-100% versus 11-13% proton alone. The dose-dependent increase of intracellular reactive oxygen species level was 12-36% at 10 Gy compared with the proton-alone control cell. Therapeutic effective drug concentration that led to 100% CTR with a proton dose of 31 Gy was measured either 41 µg Au/g tissue or 59 µg Fe/g tissue. MNP-based proton treatment increased not only percent CTR and survival in vivo but also ROS generation in vitro, suggesting tumor dose enhancement from secondary radiation as one potent pathway of therapeutic enhancement.

Photon activated therapy (PAT) using monochromatic synchrotron X-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy.

BACKGROUND: X-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy. METHODS: X-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups. RESULTS: A more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 µg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15-35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group. CONCLUSIONS: An iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer.

Cell-penetrating peptide mimicking polymer-based combined delivery of paclitaxel and siRNA for enhanced tumor growth suppression.

Cancer chemotherapy is often limited, since more than one molecule is usually involved with the cancer pathogenesis. A combination of therapeutic drugs would be a promising approach to overcome the complexity of tumors. In this study, a conjugate (DA3) of deoxycholic acid and low molecular weight polyethylenimine (PEI 1.8 kDa), which has a property that mimics that of cell penetrating peptides (CPPs), was used for simultaneous delivery of an anticancer drug and siRNA. When complexed with siRNA, DA3 showed significantly higher target gene silencing efficiency than PEI 25 kDa. The gene silencing efficiency of DA3 was maintained even in the presence of endocytosis inhibitors, suggesting that the polymeric carrier can mediate an endocytosis-independent macromolecular transduction similar to CPPs. The capability of forming a micelle-like core-shell structure enables the conjugates to encapsulate and dissolve paclitaxel (PTX), a water-insoluble drug. The drug-loaded cationic micelles can then interact with siRNA to form stable complexes (PTX/DA3/siRNA). The PTX/DA3/siRNA showed significantly enhanced inhibition of cancer cell growth. When administered into tumor-bearing animals, the PTX/DA3/siRNA demonstrated significant suppression of tumor growth, providing potential usefulness in clinical settings.

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model.

Thrombolytic effects of fucoidans were investigated in the FeCl3-induced arterial thrombus mouse model and compared with heparin and tissue plasminogen activator (t-PA). Thrombosis model was made by applying 5% FeCl3 on the carotid artery of a Balb/c mouse. Twenty minutes after complete occlusion, a couple of test agents including fucoidan were infused into each mouse group with various doses intravenously, before measuring the time to reperfusion. The occluded arteries were reperfused 37.5 ± 12.4 min after administration of unfractionated fucoidan from Undaria pinnatifida sporophylls (UPS-UF) with a dose of 100 mg/kg. In the mice given either a low-molecular-weight UPS fucoidan or fucoidan source from Fucus vesiculosus (FV-UF), reperfusion was delayed at 55.0 ± 8.0 min with a higher reperfusion effective dose (RED) of 1 g/kg or at 63.3 ± 7.2 at RED of 200 mg/kg, respectively. In the control mice given t-PA of 15 mg/kg, reperfusion occurred at 24.8 ± 6.5 min after administration. In contrast, reperfusion was not observed in the occluded mice given heparin (P < 0.001) in the range of 60-1000 mg/kg. Minimal injection of fucoidan in addition to a given t-PA-enabled restoration of blood flow in the blocked artery without reocclusion at 17.2 ± 2.3 min postinjection (P < 0.002). In conclusion, algal fucoidan has both thrombolytic activity and a stimulatory effect on the thrombolytic activity of t-PA in a dose-dependent manner at an arterial thrombosis model.

Visualization of microvascular proliferation as a tumor infiltration structure in rat glioma specimens using the diffraction-enhanced imaging in-plane CT technique.

In order to study potent microenvironments of malignant gliomas with a high- resolution x-ray imaging technique, an injection orthotopic glioma model was made using the Sprague-Dawley rat. Total brain tissue, taken out as an ex vivo model, was examined with diffraction-enhanced imaging (DEI) computed tomography (CT) acquired with a 35 keV monochromatic x-ray. In the convolution-reconstructed 2D/3D images with a spatial resolution of 12.5 × 12.5 × 25 µm, distinction among necrosis, typical ring-shaped viable tumors, edemas and healthy tissues was clearly observed near the frontal lobe in front of the rat's caudate nucleus. Multiple microvascular proliferations (MVPs) were observed surrounding peritumoral edemas as a tumor infiltration structure. Typical dimensions of tubular MVPs were 130 (diameter) ×250 (length) µm with a partial sprout structure revealed in the 3D reconstructed image. Hyperplasia of cells around vessel walls was revealed with tumor cell infiltration along the perivascular space in microscopic observations of mild MVP during histological analysis. In conclusion, DEI-CT is capable of imaging potent tumor-infiltrating MVP structures surrounding high-grade gliomas.

A novel der(16)t(3;16)(p25;q24) in a patient with ovarian cancer.

BACKGROUND: Non-random simple chromosomal aberrations in various malignancies provide important insights into the molecular pathogenesis of human cancer. Although extensive data exist on recurring chromosomal abnormalities in hematological cancer, data on individual solid tumor types remain limited. Here we present the case of a patient with ovarian cancer with a specific chromosomal abnormality. CASE REPORT: Cytogenetic analysis utilized a G-banding technique, which was performed with direct culture of the surgically removed cancer cells from a 23-year-old woman with grade II ovarian serous cystadenocarcinoma. The patient had no family history of ovarian cancer. RESULTS: We report a novel der(16)t(3;16)(p25;q24) accompanied by terminal deletion of 3p25 as the simple chromosomal aberration in this case. CONCLUSION: To the best of our knowledge, no such translocation has been previously reported. The present study supports the possible role of both del(3)(p25) and the translocation t(3;16)(p25;q24) in ovarian cancer; nevertheless, the significance of these chromosomal changes in the development of ovarian cancer remains unknown. The significance of this finding and its role in the pathogenesis of ovarian cancer requires further clarification.