Vascular Changes in Bleomycin-Induced Scleroderma

Systemic sclerosis (SSc) is characterized by vascular injury, immunological abnormalities, and fibrosis of the skin as well as various internal organs. Vascular impairment is the early manifestation and plays a fundamental role in the pathogenesis of SSc. Recent studies suggest that complex interactions among the endothelial cells, pericytes, smooth muscle cells, and fibroblasts are involved in the systemic vasculopathy in SSc, and histological feature of proliferation of vascular wall is seen in the lesional scleroderma skin at the late stage of disease. One of the most representative mouse models for scleroderma is the bleomycin-induced scleroderma; however, aspects of vascular alteration have not been described in detail so far. A number of studies have shown that bleomycin stimulates endothelial cells and fibroblasts to induce proinflammatory and fibrogenic cytokines, apoptosis, reactive oxygen species, and so on. This paper makes a focus on the vascular involvement in the bleomycin-induced murine scleroderma

Sublimation Temperature of Circumstellar Dust Particles and Its Importance for Dust Ring Formation

Dust particles in orbit around a star drift toward the central star by the Poynting-Robertson effect and pile up by sublimation. We analytically derive the pile-up magnitude, adopting a simple model for optical cross sections. As a result, we find that the sublimation temperature of drifting dust particles plays the most important role in the pile-up rather than their optical property does. Dust particles with high sublimation temperature form a significant dust ring, which could be found in the vicinity of the sun through in-situ spacecraft measurements. While the existence of such a ring in a debris disk could not be identified in the spectral energy distribution (SED), the size of a dust-free zone shapes the SED. Since we analytically obtain the location and temperature of sublimation, these analytical formulae are useful to find such sublimation evidences.Comment: 9 pages, 5 figures, to be published in Earth Planets Spac

Geomorphological Criteria for Evaluating Liquefaction Potential Considering the Level-2 Ground Motion in Japan

In response to a bitter experience in the 1995 Hyogo-ken Nambu (Kobe) earthquake, the level-2 ground motion, extraordinarily strong shaking motion that would be caused by an earthquake directly under the area such as the 1995 earthquake, has been considered in seismic design of various kind of structures in Japan, in addition to the level-l general ground motion. Geomorphological criteria in the manual for zonation on liquefaction hazard issued by Land Planning Agency, which have been used a qualitative estimate of liquefaction potential were demanded to keep up with the above-mentioned trend of the time. The purpose of this study is to develop geomorphological criteria for evaluating liquefaction potential for the level-2 ground motion as well as the level-l ground motion based on case histories in the past earthquakes. The newly developed criteria are applied to the 1948 Fukui earthquake that induced the level-2 destructive motion. A liquefaction potential map is drawn up for the Fukui Plain affected by the earthquake. The result of the assessment based on the criteria was consistent with the actual performance of the ground during the 1948 event

Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin

Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ≥ 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients

Nab-paclitaxel for the treatment of breast cancer: efficacy, safety, and approval

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel formulation of paclitaxel that does not require solvents such as polyoxyethylated castor oil and ethanol. Use of these solvents has been associated with toxic response, including hypersensitivity reactions and prolonged sensory neuropathy, as well as a negative impact in relation to the therapeutic index of paclitaxel. nab-paclitaxel displays greater antitumor activity and less toxicity than solvent-base paclitaxel. In a phase I trial of single nab-paclitaxel, the maximum tolerated dose was 300 mg/m2 with the dose limiting toxicities being sensory neuropathy, stomatitis, and superficial keratopathy. In the metastatic setting, a pivotal comparative randomized phase III study demonstrated that nab-paclitaxel (at 260 mg/m2 over 30 minutes infusion without premedication every 3 weeks) mediated a superior objective response rate and prolonged time to progression compared with solvent-based paclitaxel (at 175 mg/m2 over a 3-hour injection with standard premedication). The nab-paclitaxel-treated group showed a higher incidence of sensory neuropathy than the solvent-based paclitaxel group. However, these adverse side effects rapidly resolved after interruption of treatment and dose reduction. Weekly administration of nabpaclitaxel was also more active and displayed less toxicity compared with 100 mg/m2 docetaxel given triweekly. Nab-paclitaxel has already been approved in 42 countries for the treatment of metastatic breast cancer previously treated with anthracycline, based on confirmation of the efficacy and manageable toxicity in the metastatic setting. This review summarizes the most relevant knowledge on nab-paclitaxel for treating breast cancer in terms of clinical usefulness including efficacy and safety of this new agent