Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma

Bromodomain and extra terminal (BET) family proteins, which include BRD4, are readers of histone acetyl-lysines and key regulators of gene transcription. BRD4 inhibitors exert anti-tumor effects in various cancers, including hepatocellular carcinoma (HCC). We investigated the mechanism underlying the antitumor effects of BRD4 inhibition in HCC. We first tested the effects of the BRD4 inhibitor JQ1 in a series of 9 HCC cell lines and found that it strongly suppressed HCC cell proliferation by inducing cell cycle arrest and apoptosis. Gene expression microarray analysis revealed that JQ1 also induced marked changes in the gene expression profiles of HCC cells, and genes associated with cell cycle and apoptosis were significantly enriched among the affected genes. Notably, a number of cancer-related genes, including BCAT1, DDR1, GDF15, FANCD2, SENP1 and TYRO3, were strongly suppressed by JQ1 in HCC cells. We also confirmed BRD4 bound within the promoter regions of these genes, which suggests they are targets of BRD4 in HCC cells. JQ1 thus appears to exert its anti-tumor effects in HCC by suppressing multiple BRD4 target genes

Activated macrophages promote invasion by early colorectal cancer via an IL-1β-SAA1 axis

本研究は，低分化成分に着目して早期大腸がんの分子解析を行った．T1 大腸がんの臨床検体を用いたRNA-seqを行い，低分化成分でのserum amyloid A1（SAA1）の高発現を同定した．大腸がん細胞を用いた機能解析，マクロファージとの共培養実験，臨床検体の免疫染色解析の結果，T1大腸がんの浸潤先進部では，マクロファージとがん細胞がIL-1βとSAA1を介して相互作用することで浸潤を促進すると考えられ，SAA1が早期大腸がんの治療層別化マーカーおよび治療標的となる可能性が示唆された

Markerless Knee Joint Position Measurement Using Depth Data during Stair Walking

Climbing and descending stairs are demanding daily activities, and the monitoring of them may reveal the presence of musculoskeletal diseases at an early stage. A markerless system is needed to monitor such stair walking activity without mentally or physically disturbing the subject. Microsoft Kinect v2 has been used for gait monitoring, as it provides a markerless skeleton tracking function. However, few studies have used this device for stair walking monitoring, and the accuracy of its skeleton tracking function during stair walking has not been evaluated. Moreover, skeleton tracking is not likely to be suitable for estimating body joints during stair walking, as the form of the body is different from what it is when it walks on level surfaces. In this study, a new method of estimating the 3D position of the knee joint was devised that uses the depth data of Kinect v2. The accuracy of this method was compared with that of the skeleton tracking function of Kinect v2 by simultaneously measuring subjects with a 3D motion capture system. The depth data method was found to be more accurate than skeleton tracking. The mean error of the 3D Euclidian distance of the depth data method was 43.2 ± 27.5 mm, while that of the skeleton tracking was 50.4 ± 23.9 mm. This method indicates the possibility of stair walking monitoring for the early discovery of musculoskeletal diseases

Iatrogenic carpal tunnel syndrome induced by wrist extension for placement of an indwelling radial artery catheter: a case report

Abstract A 38-year-old man with pancreatic cancer was scheduled to undergo pancreaticoduodenectomy. He had an unremarkable past medical history. After inducing general anesthesia, a left radial arterial catheter was successfully placed at first attempt. A wrist splint was used to obtain good arterial pulse waveforms. After the operation, he was transferred to the intensive care unit. The radial artery catheter was removed on the fourth postoperative day. He experienced numbness and a tingling sensation in the left thumb, the second and third fingers, and the lateral half of the fourth finger. He was diagnosed with carpal tunnel syndrome. Diagnostic imaging revealed a swollen median nerve, but no hematoma or injury. Some studies have suggested that excessive extension of the wrist may cause neuropathy. We recommend that patients’ wrists not be over-extended, even if good arterial waveforms cannot be obtained

A Shallow Angle Short-Axis Out-of-Plane Approach Reduces the Rate of Posterior Wall Injuries in Central Venous Catheterization: A Simulation Study

The short-axis out-of-plane approach (SAX-OOP) is commonly used in ultrasound-guided internal jugular vein catheterization. However, this approach has a risk of posterior vein wall injuries. The authors hypothesized that a shallow angle of approach may reduce the rate of posterior wall injuries compared with the conventional steep angle approach. The present study aimed to evaluate whether a difference in the angle of approach of the needle affects the rate of posterior wall injuries. The present study was a randomized crossover-controlled trial involving 40 medical residents, conducted in the clinical training center at a hospital with a residency program. The primary outcome measure was the rate of posterior vessel wall injuries. Subjects received a didactic lecture during which the instructors taught three SAX-OOP techniques including the conventional free-hand method (procedure C), a needle navigation system (procedure N), and a shallow puncture angle using a guidance system (procedure S). Participants were trained in these approaches under supervision and each technique tested in a simulation environment. Thirty-four of 40 residents had no previous experience with central venous catheterization and were included in the final analysis. The rate of posterior vessel wall injuries in procedure S (9%) was significantly lower than using the other approaches (procedure C, 53%; procedure N, 41%). In conclusion, a shallow angle of approach using the SAX-OOP technique resulted in significantly fewer posterior vein wall injuries in central venous catheterization compared with steep angle techniques