Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communication

Background: Homeobox B9 (HOXB9), a transcriptional factor, regulates developmental processes and tumor progression and has recently been recognized as one of important transcriptional factors related to angiogenesis. This study aimed to investigate the role of HOXB9 in tumorigenesis and angiogenesis. Methods: We examined the expression of HOXB9 in colorectal cancer using qPCR and in situ hybridization. We also examined the effect of HOXB9 overexpression in colorectal cancer using a proliferation assay, ELISA, a multiplex assay, and xenograft models. The clinical significance of HOXB9 was statistically evaluated in resected specimens. Results: HOXB9 was expressed in colorectal cancer specimens. HOXB9 induced angiogenesis and tumor proliferation in vitro, which resulted in high tumorigenicity in vivo and poor overall survival. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, remarkably suppressed tumor proliferation by inhibiting angiogenesis in HOXB9-overexpressing xenografts, and it improved overall survival and provided prolonged progression-free survival in HOXB9-overexpressing patients. A comprehensive multiplex assay of the supernatant of cancer cells co-cultured with human vascular endothelial cells and fibroblasts indicated significantly higher interleukin-6 (IL6) levels than those in the supernatant of monocultured cells. HOXB9 overexpression in clinical specimens was significantly correlated with increased IL6 expression. An IL6-neutralizing antibody inhibited VEGF secretion and tumor proliferation in the co-culture system. Conclusions: HOXB9 promotes the secretion of angiogenic factors, including VEGF, to induce tumor proliferation through microenvironmental production of cytokines including IL6 signaling. Moreover, silencing of VEGF or IL6 terminates cytokine release in tumor microenvironment. Thus, HOXB9 and IL6 may be potential biomarkers for bevacizumab treatment

Open Access

Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communicatio

Guideline from Japanese Society of Echocardiography : 2018 focused update incorporated into Guidance for the Management and Maintenance of Echocardiography Equipment

Echocardiography plays a pivotal role as an imaging modality in the modern cardiology practice. Information derived from echocardiography is definitely helpful for a patient care. The Japanese Society of Echocardiography has promoted echocardiography for a routine clinical and research use. One of the missions of the Society is to provide information that is useful for high-quality examinations. To ensure it, we believe equipment in good conditions and a comfortable environment are important for both a patient and an examiner. Thus, the Committee for Guideline Writing, the Japanese Society of Echocardiography published brief guidance for the routine use of echocardiography equipment in 2015. Recently, the importance of international standardization has been emphasized in the medical laboratories. Accordingly, the committee has revised and updated our guidance for the routine use of echocardiography equipment

Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements

AbstractAn association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements

Suzaku observations of the hard X-ray variability of MCG-6-30-15: the effects of strong gravity around a Kerr black hole

Suzaku has, for the first time, enabled the hard X-ray variability of the Seyfert 1 galaxy MCG-6-30-15 to be measured. The variability in the 14-45 keV band, which is dominated by a strong reflection hump, is quenched relative to that at a few keV. This directly demonstrates that the whole reflection spectrum is much less variable than the power-law continuum. The broadband spectral variability can be decomposed into two components - a highly variable power-law and constant reflection - as previously inferred from other observations in the 2-10 keV band. The strong reflection and high iron abundance give rise to a strong broad iron line, which requires the inner disc radius to be at about 2 gravitational radii. Our results are consistent with the predictions of the light bending model which invokes the very strong gravitational effects expected very close to a rapidly spinning black hole.Comment: accepted for publication in PASJ Suzaku special issu

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray