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Notch signaling is one of the most common drivers of carcinogenesis in many types of cancers, including hepatocellular carcinoma (HCC); however, it occasionally suppresses tumor progression. Moreover, it is virtually unknown how different sets of Notch ligands and receptors regulate the HCC development. In this study, we demonstrate that the expression of the Notch ligands, Delta-like 4 (Dll4) and Jagged-1 (Jag1), is upregulated during diethylnitrosamine-induced hepatocarcinogenesis. Dll4 is detected in the preneoplastic hepatocytes and HCC cells, but not in the normal hepatocytes, while Jag1 is expressed in the desmin-positive mesenchymal cells. Hepatocyte-specific Dll4 knockout abolishes the Notch1 signaling and suppresses the tumor progression. In contrast, Jag1 deletion induces the ectopic expression of Dll4 in hepatocytes along with the loss of Notch2 signaling, leading to the tumor progression. These results indicate that the two distinct Notch signals, Dll4/Notch1 and Jag1/Notch2, are antagonistic to each other, exerting opposite effects on HCC progression., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Background/aim: Traditionally, the radiotherapy of oesophageal cancer has been conformal radiotherapy (CRT). We sought to compare dosimetric parameters of conformal radiotherapy (CRT) with those of two treatment planning systems for hybrid-volumetric modulated arc therapy (h-VMAT) for the treatment of oesophageal cancer., Patients and Methods: In 11 patients, we compared: i) planning target volume coverage, ii) dose to organs at risk, and iii) the dose rate (DR) of the three techniques. We evaluated two treatment planning systems: i) Eclipse and ii) RayStation., Results: The Conformity Index of the CRT plan was significantly higher for the h-VMAT plans, compared to all other parameters. Normal lung tissue volumes receiving >5, 13, or 20 Gy were lower with the RayStation plan compared to Eclipse. The volume of cardiac tissue receiving >40 Gy was highest with the CRT plan. The minimum DR in VMAT was lowest for the RayStation plan (49.5 MU/min)., Conclusion: The h-VMAT plan using RayStation is the appropriate choice for reducing lung dose., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study was to clarify the influence of complications of diabetes on the exercise tolerance of patients with heart failure., Methods: The subjects of this study were 69 patients (44 men; mean age: 62.2 ± 13.4 years) who were hospitalized and diagnosed with heart failure between November 2016 and November 2017. The subjects all took part in a cardiopulmonary exercise test. The patients' medical background, indexes obtained from lower-limb muscle strength and the cardiopulmonary exercise test, heart rate response indexes [Δ heart rate (ΔHR)], and autonomic nervous activities were measured, and these individual indexes were compared between the diabetic group and the non-diabetic group., Results: Compared with the non-diabetic group, the peak oxygen uptake (peak V̇O 2 ) and ΔHR in the diabetic group were significantly lower (13.0 ± 2.2 vs. 14.9 ± 4.4 ml/kg/min and 27.2 ± 11.7 vs. 36.7 ± 14.7 bpm, respectively) (p<0.05). Regarding the autonomic nervous activity during the cardiopulmonary exercise test in the diabetic group, there was a significant decrease of parasympathetic nerve activity and a significant lack of increase in sympathetic nerve activity (p<0.05)., Conclusions: Patients with heart failure and diabetes had lower levels of exercise tolerance, as compared with patients without complications. It was suggested that the decrease in heart rate response was due to the decrease of autonomic nervous activity and that this may play a role in reduced exercise tolerance., Competing Interests: There is no conflict of interest to disclose., (2019, JAPANESE PHYSICAL THERAPY ASSOCIATION.)

We sought to validate new couch modeling optimization for tomotherapy planning and delivery. We constructed simplified virtual structures just above a default setting couch through a planning support system (MIM Maestro, version 8.2, MIM Software Inc, Cleveland, OH, USA). Based on ionization chamber measurements, we performed interactive optimization and determined the most appropriate physical density of these virtual structures in a treatment planning system (TPS). To validate this couch optimization, Gamma analysis and these statistical analyses between a three-dimensional diode array QA system (ArcCHECK, Sun Nuclear, Melbourne, FL, USA) results and calculations from ionization chamber measurements were performed at 3%/2 mm criteria with a threshold of 10% in clinical QA plans. Using a virtual model consisting of a center slab density of 4.2 g/cm 3 and both side slabs density of 1.9 g/cm 3 , we demonstrated close agreement between measured dose and the TPS calculated dose. Agreement was within 1% for all gantry angles at the isocenter and within 2% in off-axis plans. In validation of the couch modeling in a clinical QA plan, the average gamma passing rate improved approximately 0.6%-5.1%. It was statistically significant (P < 0.05) for all treatment sites. We successfully generated an accurate couch model for a TomoTherapy TPS by interactively optimizing the physical density of the couch using a planning support system. This modeling proved to be an efficient way of correcting the dosimetric effects of the treatment couch in tomotherapy planning and delivery., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The liver is well known to possess high regenerative capacity in response to partial resection or tissue injury. However, liver regeneration is often impaired in the case of advanced liver fibrosis/cirrhosis when mature hepatocytes can hardly self-proliferate. Hepatic progenitor cells have been implicated as a source of hepatocytes in regeneration of the fibrotic liver. Although alpha-fetoprotein (AFP) is known as a clinical marker of progenitor cell induction in injured/fibrotic adult liver, the origin and features of such AFP-producing cells are not fully understood. Here, we demonstrate a unique and distinct AFP-expressing cell population that is induced by the Jagged1/Notch2 signal in murine fibrotic liver. Following repeated carbon tetrachloride injections, a significant number of AFP-positive cells with high proliferative ability were observed along the fibrous septa depending on the extent of liver fibrosis. These AFP-positive cells exhibited features of immature hepatocytes that were stained positively for hepatocyte-lineage markers, such as albumin and hepatocyte nuclear factor 4 alpha, and a stem/progenitor cell marker Sox9. A combination of immunohistological examination of fibrotic liver tissues and coculture experiments with primary hepatocytes and hepatic stellate cells indicated that increased Jagged1 expression in activated hepatic stellate cells stimulated Notch2 signaling and up-regulated AFP expression in adjacent hepatocytes. The mobilization and proliferation of AFP-positive cells in fibrotic liver were further enhanced after partial hepatectomy, which was significantly suppressed in Jagged1-conditional knockout mice. Finally, forced expression of the intracellular domain of Notch2 in normal liver induced a small number of AFP-expressing hepatocytes in vivo. Conclusion : Insight is provided into a novel pathophysiological role of Jagged1/Notch2 signaling in the induction of AFP-positive cells in fibrotic liver through the interaction between hepatocytes and activated hepatic stellate cells. ( Hepatology Communications 2017;1:215-229).

Purpose: Flat panel detector (FD)-equipped angiography machines are increasingly used for neuro-angiographic imaging. During intracranial stent-assisted coil embolization procedures, it is very important to clearly and quickly visualize stent shape after deployment in the vessel. It is necessary to quickly visualize stents by cone-beam computed tomography (CBCT). The aim of this study was to compare CBCTs at 10 and 20 s, and to confirm that this method is useful for neuro-endovascular treatment procedures., Materials and Methods: We treated 30 patients with wide-necked intracranial aneurysms with a flexible, self-expanding neurovascular stent and subsequent aneurysm embolization with platinum micro-coils. We performed the CBCT after stent deployment. We compared the 10 s and 20 s CBCTs, using the full width one-half maximum (FWHM) visualization., Results: Accurate stent placement with subsequent coil occlusion of the aneurysms was feasible in all patients. Stent struts were clearly visualized on both 10 s and 20 s CBCTs. Importantly, 10 s CBCT can reduce the radiation dose by about 42%, compared with 20 s CBCT. Performing 10 s CBCT with a 14% dilution of the contrast medium may significantly improve image acquisition during stent-assisted coil embolization., Conclusions: Reduced-dose, 10 s CBCT can visualize stents in clinical cases, while significantly reducing radiation exposure., (© The Author(s) 2016.)

To establish a concise and rapid procedure to analyze hexabromocyclododecane (HBCD) diastereomers in flame-retarded textiles, three different methods of extraction-Soxhlet, ultrasonic, and soaking extractions with toluene and dichloromethane (DCM)-were compared. During Soxhlet extraction using toluene, the percent contribution of alpha-HBCD to total HBCDs increased slightly and that of gamma-HBCD decreased, indicating that gamma-HBCD was isomerized to some extent at the boiling point of toluene (110.6 degrees C). For ultrasonic extraction, the temperature of the water bath can easily increase over time during the procedure, which might lead to undesirable effects. Therefore, we considered soaking extraction with DCM to be the most facile procedure to analyze HBCD diastereomers in textiles. Using the method established in this study, commercially available textiles in Japan (n=10) were analyzed to understand the actual composition of HBCD contents and its diastereomer profiles. With the exception of one textile sample, HBCDs were detected in all the samples analyzed, with concentrations ranging from 22000 to 43000 mg kg(-1) (i.e. 2.2-4.3%). We found a higher proportion of the alpha-diastereomer in most textile products compared with that of commercial HBCD mixtures, indicating that gamma-HBCD isomerized to alpha-diastereomer by heating processes to incorporate the commercial formulation into treated materials or that the alpha-diastereomer preferentially absorbed onto textile materials during the manufacturing of flame-retarded consumer products.