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PAR1b is a cytoplasmic serine/threonine kinase that controls cell polarity and cell–cell interaction by regulating microtubule stability while mediating cytoplasmic-to-nuclear translocation of BRCA1. PAR1b is also a cellular target of the CagA protein of Helicobacter pylori, which leads to chronic infection causatively associated with the development of gastric cancer. The CagA-PAR1b interaction inactivates the kinase activity of PAR1b and thereby dampens PAR1b-mediated BRCA1 phosphorylation, which reduces the level of nuclear BRCA1 and thereby leads to BRCAness and BRCAness-associated genome instability underlying gastric carcinogenesis. While PAR1b can multimerize within the cells, little is known about the mechanism and functional role of PAR1b multimerization. We found in the present study that PAR1b was multimerized in vitro by binding with nucleic acids (both single- and double-stranded DNA/RNA) via the spacer region in a manner independent of nucleic-acid sequences, which markedly potentiated the kinase activity of PAR1b. Consistent with these in vitro observations, cytoplasmic introduction of double-stranded DNA or expression of single-stranded RNA increased the PAR1b kinase activity in the cells. These findings indicate that the cytoplasmic DNA/RNA contribute to nuclear accumulation of BRCA1 by constitutively activating/potentiating cytoplasmic PAR1b kinase activity, which is subverted in gastric epithelial cells upon delivery of H. pylori CagA oncoprotein. [ABSTRACT FROM AUTHOR]

Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE‐MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype. A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1‐min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann–Whitney U‐test was used for the statistical analysis. The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A‐like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05). The sigmoid model analysis of breast DCE‐MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A‐like breast cancer. [ABSTRACT FROM AUTHOR]

Summary Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the East Asian CagA-specific EPIYA-D segment binds to the N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders of magnitude greater than Western CagA-specific EPIYA-C. This high-affinity binding is achieved via cryptic interaction between Phe at the +5 position from phosphotyrosine in EPIYA-D and a hollow on the N-SH2 phosphopeptide-binding floor. Also, duplication of EPIYA-C in Western CagA, which increases gastric cancer risk, enables divalent high-affinity binding with SHP2 via N-SH2 and C-SH2. These strong CagA bindings enforce enzymatic activation of SHP2, which endows cells with neoplastic traits. Mechanistically, N-SH2 in SHP2 is in an equilibrium between stimulatory “relaxed” and inhibitory “squeezed” states, which is fixed upon high-affinity CagA binding to the “relaxed” state that stimulates SHP2. Accordingly, East Asian CagA and Western CagA exploit distinct mechanisms for SHP2 deregulation. [ABSTRACT FROM AUTHOR]

Purpose: To assess the usefulness of transcatheter arterial embolization (TAE) for the hepatic arterial injury related to percutaneous transhepatic portal intervention (PTPI).Materials and Methods: Fifty-four patients, 32 males and 22 females with a median age of 68 years (range 43-82 years), underwent PTPI. The procedures consisted of 33 percutaneous transhepatic portal vein embolizations, 19 percutaneous transhepatic variceal embolizations, and 2 percutaneous transhepatic portal venous stent placements. Two patients with gastric varices underwent percutaneous transhepatic variceal embolization twice because of recurrence. Therefore, the total number of procedures was 56. Among them, hepatic arterial injury occurred in 6 PTPIs in 5 patients, and TAE was performed. We assessed technical success, complications related to TAE, and clinical outcome. Technical success was defined as the disappearance of findings due to hepatic arterial injury on digital subtraction angiography.Results: As hepatic arterial injuries, 4 extravasations and 2 arterioportal shunts developed. All TAEs were performed successfully. The technical success rate was 100 %. Complication of TAE occurred in 5 of 6 TAEs; 3 were focal liver infarction, not requiring further treatment, and 2 were biloma that required percutaneous drainage. Five TAEs in 4 patients were performed immediately after the PTPI, and these 4 patients were alive. However, one TAE was performed 10 h later, and the patient died due to multiple organ failure 2 months later although TAE was successful.Conclusion: TAE is a useful treatment for hepatic arterial injury related to PTPI. However, it should be performed at an early stage. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic ability of planar images (PI) and images obtained by a computer-aided diagnosis (CAD) system (Viewer for Standardized Bone Scintigraphies; VSBONE) of whole-body bone scintigraphy for detecting bone metastases in breast cancer patients. Methods: 81 women (median: 56 years; range: 32-79) with a history of breast cancer were included in this study. They underwent whole-body bone scintigraphy after intravenous injection of 740 MBq technetium-99m hydroxymethylene diphosphonate. A total of 1066 bones (162 regions of the skull, 657 regions of the spine and pelvis, 223 regions of the sternum and rib, 18 regions of the upper extremities, and 6 regions of the lower extremities) were analyzed. The PI alone, VSBONE images alone, and both PI and VSBONE images (PI + VSBONE) were interpreted independently by two radiologists to diagnose bone metastases, which were then confirmed by magnetic resonance imaging. The sensitivity and specificity for each modality were analyzed using Fisher's exact and McNemar tests. Inter-reviewer agreement was evaluated using a kappa statistic. Results: Bone metastases were confirmed in 43 patients with 442 positive lesions. The average sensitivity of PI, VSBONE images, and PI + VSBONE images was 40.8, 50.2, and 61.8 %, respectively. The average specificity was 97.8, 97.5, and 97.6 %, respectively. The kappa scores were 0.62 for PI, 0.69 for VSBONE, and 0.77 for PI + VSBONE. Conclusions: VSBONE was superior to PI in regard to sensitivity for detecting bone metastases in breast cancer patients. However, an improved CAD system is required to decrease the number of false-negative results. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors. Methods and Materials: Fifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy. Results: All 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration. Conclusion: Transarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors. [ABSTRACT FROM AUTHOR]

The enzyme activity synthesizing poly-β-hydroxybutyrate (PHB) was mainly localized in the PHB-containing particulate fraction of Zoogloea ramigera I-16-M, when it grew flocculatedly in a medium supplemented with glucose. On the other hand, the enzyme activity remained in the soluble fraction, when the bacterium grew dispersedly in a glucose-starved medium. The soluble PHB synthase activity became associated with the particulate fraction as PHB synthesis was initiated on the addition of glucose to the dispersed culture. Conversely, the enzyme activity was released from the PHB-containing granules to the soluble fraction when the flocculated culture was kept incubated without supplementing the medium with glucose. PHB synthase was also incorporated into the newly formed PHB fraction when partially purified soluble PHB synthase was incubated with d(-)-β-hydroxybutyryl CoA in vitro. Although attempts to solubilize the particulate enzyme were unsuccessful, and the soluble enzyme became extremely unstable in advanced stages of purification, both PHB synthases had the same strict substrate specificity for d(-)-β-hydroxybutyryl CoA, and showed the same pH optimum at 7.0. [ABSTRACT FROM AUTHOR]

We present a case of acute small-bowel bleeding from the collateral artery of the superior mesenteric-left deep circumflex iliac artery that was successfully managed by transarterial coil embolization. [ABSTRACT FROM AUTHOR]