Hiroki Nagai

MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis.

BACKGROUND Abnormal miRNA expression was recently implicated in the metastasis of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation of the invasion-metastasis cascade involves epithelial-mesenchymal transition (EMT). Our aim was to clarify how miRNA, especially miR-155-5p misexpression contributes to OSCC metastasis through EMT. METHODS We collected tumor samples from 73 subjects with OSCC. The samples were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and correlations between miR-155-5p levels and clinical characteristics were investigated. OSCC cell lines were analyzed by miRNA microarray and by transfection with a miR-155-5p mimic or inhibitor, followed by proliferation and wound-healing migration assays. qRT-PCR analyses of EMT makers in cells transfected with miR-155-5p inhibitor were performed. RESULTS We found high miR-155-5p expression in tissue samples from subjects with OSCC that had metastasized to cervical lymph nodes. HSC-3 cells also strongly expressed miR-155-5p. The epithelial marker E-cadherin was strongly expressed in HSC-3 cells transfected with miR-155-5p inhibitor, and we observed elevated SOCS1 and decreased STAT3 expression in these cells. CONCLUSIONS Our results suggest that miR-155-5p causes OSCC to metastasize, and could serve as a novel therapeutic target for OSCC.

Experimental Investigation of Thermal Shock Wave Induced by Gas Dynamic Shock Wave Impingement

The thermal shock wave in He II is investigated by measuring the temperature variation with a superconductive temperature sensor. It is generated by the impingement of a gas dynamic shock wave onto a He II free surface in the newly developed superfluid shock tube facility. The profile of thermal shock is found to be of a single triangular waveform with a limited shock strength. It is suggested from the experimental result that a thermal shock wave is generated not at the moment of the impingement nor propagates from the original free surface, but it is generated at slightly lower than the original free surface and a little later than the impingement. This means that a thermal shock wave is generated at the lower end of a thermal boundary layer after it is established. In the thermal boundary layer with a thickness of several mm, the thermodynamic state changes from supercritical at the original free surface to compressed He II via compressed He I. It is sometimes found in the experiments near lambda temperatures, that no thermal shock wave is detected in shock compressed He II. It can be understood that shock compression makes He II convert to He I where no thermal shock wave is excited.

Development of superfluid shock tube facility

The superfluid shock tube facility has been developed as a versatile tool for general researches in low-temperature thermo-fluid dynamic phenomena. The shock tube was designed to be operated with the He II-filled test section immersed in superfluid helium. A special feature of the facility is that the gas dynamic shock tube is driven and controlled with a quick-opening valve (MO-valve). It enables a synchronized discharge of a shock wave with other target transient phenomena. Some wave phenomena such as a thermal shock and a compression shock waves in superfluid helium, and phase transition phenomena across the λ-line (He I-He II) and across the He II-solid helium phase boundary can be investigated by impinging a gas dynamic shock wave onto a vapor-He II free surface in the test section. The target physical phenomena in He II are measured by pressure transducers and superconductive temperature sensors, by applying laser beam refraction method, and with the aid of some optical visualization methods. In the present study, the general thermo-fluid dynamic performance are investigated to verify the validity in wide range of experimental researches.

MicroRNA-205-5p suppresses the invasiveness of oral squamous cell carcinoma by inhibiting TIMP‑2 expression

MicroRNAs (miRNAs or miRs) play important roles in carcinogenesis. The miRNA, miR-205-5p, has been reported to suppress the growth of various types of tumor; however, its functional contribution to oral squamous cell carcinoma (OSCC) is not yet clear. Thus, this study was conducted to determine the miRNA expression signatures in OSCC and to investigate the functional role of miR‑205‑5p in OSCC cells. We measured miR‑205‑5p expression by RT-qPCR, and examined the function of miR‑205‑5p by transfecting a miR‑205‑5p mimic or inhibitor into OSCC cells and measuring cell proliferation, migration and invasiveness. Genes targeted by miR‑205‑5p were identified using the TargetScan database and verified by western blot analysis, luciferase reporter assay and ELISA. We found that miR‑205‑5p was significantly downregulated in OSCC cell lines and tissue specimens. Following transfection of miR‑205‑5p mimic or inhibitor into the cancer cell lines, miR‑205‑5p overexpression significantly suppressed cancer cell migration and invasion. We further demonstrated that miR‑205‑5p directly targeted and regulated the tissue inhibitor of metalloproteinases‑2 (TIMP‑2) gene. The silencing of TIMP‑2 suppressed cancer cell invasion and the activation of pro‑matrix metalloproteinase‑2 (pro‑MMP‑2). These results suggest that TIMP‑2 promotes tumor progression, and that miR‑205‑5p directly regulates TIMP‑2, thereby suppressing pro‑MMP‑2 activation and inhibiting OSCC cell invasiveness. Our data describing the pathways regulated by miR‑205‑5p provide new insight into the mechanisms responsible for OSCC development and metastasis.

Expression of autophagy-related markers at the surgical margin of oral squamous cell carcinoma correlates with poor prognosis and tumor recurrence

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, and is associated with poor prognosis. Autophagy is a programmed cell survival mechanism involved in physiologic processes and various diseases including cancer. However, the relationship between autophagy and cancer is controversial. Several studies have claimed that the expression of autophagy-related proteins, namely microtubule-associated protein light chain3 (LC3) and p62/SQSTM1 (p62), is associated with poor prognosis in OSCC. In this study, we evaluated the expression of the autophagy-related markers LC3A/B and p62 by immunohistochemistry in 71 OSCC patient samples, especially focusing on surgical margins. Results were correlated with clinical characteristics. The expression of LC3A and LC3B was correlated with tumor recurrence and poor overall survival based on multivariate analysis, whereas the expression of p62 was correlated with only tumor recurrence and not prognosis. Thus, we suggest that the expression of autophagy-related markers at the surgical margins might be an indicator of local recurrence and poor prognosis in human OSCC. These results will aid in the development of new therapeutics and diagnostics for OSCC.

A Case of Brain Abscess Caused by Medication-Related Osteonecrosis of the Jaw

Reports of brain abscesses caused by medication-related osteonecrosis of the jaw (MRONJ) are very rare. We here present the case of a 76-year-old man with terminal-stage prostatic carcinoma and a brain abscess caused by MRONJ at the maxilla. The patient had been treated with zoledronic acid and denosumab for bone metastasis. For the brain abscess, an antibiotic regimen based on ceftriaxone and metronidazole and a sequestrectomy contributed to a successful outcome. In the case of maxillary MRONJ extending to the maxillary sinus, active resection of the infected bone should be considered to prevent the spread of the infection beyond the maxillary sinus, into the ethmoid sinus, and into the brain.

STEADY AND TRANSIENT BEHAVIOR OF A DOUBLE-CONDENSER DESIGN LHP FOR MAXI

A loop heat pipe (LHP) is used as the heat transport device to reject heat from the Monitor of All-sky X-ray Image (MAXI). Since this LHP was designed exclusively for the MAXI system, it is different from conventional LHPs in configuration , a double -condenser design. We experimentall y investigated the effects of the particular design of this LHP on the heat transfer performance by using the LHP Ground Test Unit (GTU) on the ground. The steady heating experiment was carried out to investigate the steady state performance of LHP. When the two condensers were cooled at different temperatures under a steady heating condition, a quasi-periodic temperature oscillation was observed in the evaporator and accumulator area. We experimentally investigated the cause and mechanism of the temperature oscillation.

Study of shock waves and phase transition in He II by using a superfluid shock tube facility

In the experimental study, we focus on the thermo-fluid dynamics of shock waves and the lambda phase transition, He II to He I, induced by shock compression utilizing the newly developed superfluid shock tube facility. In the experimental facility, a compression shock wave is generated in He II by the impingement of a gas dynamic shock wave propagating through the helium vapor onto a He II free surface. He II can be shockcompressed to convert to He I across the lambda line in the case of He II initially at temperatures rather close to the lambda temperature. The highly transient lambda phase transition is detected very rapidly (a few μsec) by a superconductive temperature sensor, where the temperature variation is positive, in striking contrast to the temperature drop that occurs during He II shock compression without the lambda transition. Photographs of these phenomena are taken by the Schlieren visualization method.

Study of thermal shock wave in shock-compressed He II induced by gas dynamic shock wave impingement

Strong thermal shock waves induced by the impingement of a gas dynamic shock wave onto a He II free surface in the superfluid shock tube facility were investigated by measuring temperature variation with superconductive temperature sensors and by Schlieren visualization method with an ultra high-speed video camera (40,500 pictures/sec). The heat transfer from shock-compressed high temperature vapor to He II forming a thermal shock wave is considered. The temperature rise ratio of an induced thermal shock to that of an incident gas dynamic shock wave was found to be very small, as small as 0.003 at 1.80 K. It is seen that the most part of the heat do not be transmitted into bulk He II because a high density quantized vortex layer is rapidly developed in a thermal boundary layer in the immediate vicinity of the vapor-He II interface. The existence of a thermal boundary layer with a large temperature gradient in which the physical state varies from supercritical helium to He II temperature and the rapid grow...