Summary
Background
The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy ...(S + RT).
Objectives
To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy.
Methods
We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel).
Results
The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5‐year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse‐free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long‐term survival after T + RT.
Conclusions
From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.
What's already known about this topic?
The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm, has been reported to be dismal, even after conventional surgery and radiotherapy.
What does this study add?
The treatment of CAS with chemoradiotherapy with taxane achieved a high response ratio (14 complete remissions and one partial remission), with significant improvement of overall survival compared with surgery and radiotherapy.
Continuation of chemotherapy after chemoradiotherapy offered significantly prolonged survival than chemoradiotherapy alone.
The Small Carry-on Impactor (SCI) equipped on
Hayabusa2
was developed to produce an artificial impact crater on the primitive Near-Earth Asteroid (NEA) 162173 Ryugu (Ryugu) in order to explore the ...asteroid subsurface material unaffected by space weathering and thermal alteration by solar radiation. An exposed fresh surface by the impactor and/or the ejecta deposit excavated from the crater will be observed by remote sensing instruments, and a subsurface fresh sample of the asteroid will be collected there. The SCI impact experiment will be observed by a Deployable CAMera 3-D (DCAM3-D) at a distance of ∼1 km from the impact point, and the time evolution of the ejecta curtain will be observed by this camera to confirm the impact point on the asteroid surface. As a result of the observation of the ejecta curtain by DCAM3-D and the crater morphology by onboard cameras, the subsurface structure and the physical properties of the constituting materials will be derived from crater scaling laws. Moreover, the SCI experiment on Ryugu gives us a precious opportunity to clarify effects of microgravity on the cratering process and to validate numerical simulations and models of the cratering process.
A projectile accelerated by the Hayabusa2 Small Carry-on Impactor successfully produced an artificial impact crater with a final apparent diameter of 14.5 ± 0.8 m on the surface of the near-Earth ...asteroid 162173 Ryugu on April 5, 2019. At the time of cratering, Deployable Camera 3 took clear time-lapse images of the ejecta curtain, an assemblage of ejected particles forming a curtain-like structure emerging from the crater. Focusing on the optical depth of the ejecta curtain and comparing it with a theoretical model, we infer the size of the ejecta particles. As a result, the typical size of the ejecta particles is estimated to be several centimeters to decimeters, although it slightly depends on the assumed size distribution. Since the ejecta particles are expected to come from a depth down to ~1 m, our result suggests that the subsurface layer of Ryugu is composed of relatively small particles compared to the uppermost layer on which we observe many meter-sized boulders. Our result also suggests a deficit of particles of less than ~1 mm in the subsurface layer. These findings will play a key role in revealing the formation and surface evolution process of Ryugu and other small Solar System bodies.
Summary
Background
LL‐37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis ...(SSc).
Objectives
To elucidate the potential role of LL‐37 in SSc.
Methods
The expression of target molecules was evaluated by immunostaining and quantitative reverse‐transcription real‐time polymerase chain reaction in human and murine skin. The mechanisms regulating LL‐37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL‐37 levels were determined by enzyme‐linked immunosorbent assay.
Results
In SSc lesional skin, LL‐37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon‐α expression, possibly reflecting LL‐37‐dependent induction of interferon‐α. In SSc animal models, bleomycin‐treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL‐37, similar to that of LL‐37 in SSc lesional skin. Furthermore, Fli1+/− mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL‐37 gene) promoter and Fli1 deficiency‐dependent induction of LL‐37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL‐37 levels significantly higher than in healthy controls. Furthermore, serum LL‐37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without.
Conclusions
LL‐37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.
What's already known about this topic?
LL‐37, an antimicrobial peptide, has been shown to be upregulated in systemic sclerosis dermal fibroblasts.
LL‐37 potentially contributes to dermal fibrosis through its antiapoptotic effect on those cells.
What does this study add?
LL‐37 potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in systemic sclerosis.
This further supports the critical role of antimicrobial peptides in the development of autoimmune and inflammatory diseases.
What is the translational message?
LL‐37 induction due to Fli1 deficiency in endothelial cells supports the notion that Fli1 deficiency is a key predisposing factor in the pathogenesis of systemic sclerosis.
This has recently been demonstrated by the establishment of a new systemic sclerosis animal model, with mice double heterozygous for the Klf5 and Fli1 genes.
Strong spin polarization of the photocurrent from bulk continuum states of Bi(111) is experimentally observed. On the basis of ab initio one-step photoemission theory the effect is shown to originate ...from the strong polarization of the initial states at the surface and to be the result of the surface sensitivity of photoemission. Final state effects cause deviations of the k{∥} dependence of polarization from strictly antisymmetric relative to Γ.
Experiments on crater formation in the strength regime were conducted using projectiles of various shapes with an aspect ratio of ~ 1, including both solid and hollow interiors. The surface diameter, ...inner (pit) diameter, and depth of the craters on basalt and porous gypsum targets were measured. Using the bulk density of the projectile, the surface diameter and depth for basalt and the pit diameter and depth for porous gypsum were scaled using the pi-scaling law for crater formation in the strength regime. The numerical code iSALE was used to simulate the impact of projectiles of various shapes and interior structure with similar bulk densities. Results show that the distributions of the maximum (peak) pressure experienced and particle velocity in the targets were similar regardless of projectile shape and interior structure, implying that the dimensions of the final craters were almost identical. This is consistent with the experimental results. Thus, we conclude that the size of the craters formed by the impact of projectiles with different shape and interior structure can be scaled using a conventional scaling law in the strength regime, using bulk density as projectile density.
Graphical abstract
Summary
Background
Lipocalin‐2 is an adipocytokine implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease.
Objectives
To investigate the role of ...lipocalin‐2 in systemic sclerosis (SSc).
Materials and methods
Serum lipocalin‐2 levels were determined by enzyme‐linked immunosorbent assay in 50 patients with SSc and 19 healthy subjects. Lipocalin‐2 expression was evaluated in the skin of patients with SSc and bleomycin (BLM)‐treated mice and in Fli1‐deficient endothelial cells by reverse transcriptase‐real time polymerase chain reaction, immunoblotting and/or immunohistochemistry.
Results
Although serum lipocalin‐2 levels were comparable between patients with SSc and healthy controls, the prevalence of scleroderma renal crisis was significantly higher in patients with SSc with elevated serum lipocalin‐2 levels than in those with normal levels. Furthermore, serum lipocalin‐2 levels inversely correlated with estimated glomerular filtration rate in patients with SSc with renal dysfunction. Among patients with SSc with normal renal function, serum lipocalin‐2 levels positively correlated with skin score in patients with diffuse cutaneous SSc with disease duration of < 3 years and inversely correlated with estimated right ventricular systolic pressure in total patients with SSc. Importantly, in SSc lesional skin, lipocalin‐2 expression was increased in dermal fibroblasts and endothelial cells. In BLM‐treated mice, lipocalin‐2 was highly expressed in dermal fibroblasts, but not in endothelial cells. On the other hand, the deficiency of transcription factor Fli1, which is implicated in SSc vasculopathy, induced lipocalin‐2 expression in cultivated endothelial cells.
Conclusions
Lipocalin‐2 may be involved in renal dysfunction and dermal fibrosis of SSc. Dysregulated matrix metalloproteinase‐9/lipocalin‐2‐dependent angiogenesis due to Fli1 deficiency may contribute to the development of pulmonary arterial hypertension associated with SSc.
What's already known about this topic?
Adipokines have been shown to play various important roles in systemic sclerosis (SSc).
Lipocalin‐2 is a member of the adipokines, which are implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease.
What does this study add?
Lipocalin‐2 potentially contributes to the development of skin sclerosis, pulmonary arterial hypertension and renal damage in SSc, further supporting the critical roles of adipokines in the pathogenesis of this disease.
Summary
Background
Interleukin (IL)‐33 is a recently identified cytokine, which is a member of the IL‐1 family and binds to a heterodimeric receptor comprising ST2 (suppression of tumorigenicity 2) ...and IL‐1 receptor accessory protein. Serum levels of IL‐33 have been reported to be upregulated in various T helper (Th)1/Th17‐mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease. IL‐33 expression is increased in lesional skin in patients with psoriasis, but serum levels in patients with psoriasis have not yet been studied.
Aim
To study serum IL‐33 levels in patients with psoriasis, a Th1/Th17‐mediated skin disease, before and after anti‐tumour necrosis factor (TNF)‐α therapy.
Methods
Serum IL‐33 levels were measured in patients with psoriasis vulgaris (PV), psoriatic arthritis (PsA) or pustular psoriasis (PP), and compared with those of healthy controls. Associations between serum IL‐33 levels and serum TNF‐α, IL‐6, vascular endothelial growth factor and C‐reactive protein levels were also studied. In addition, the effect of IL‐33 stimulation on IL‐6, IL‐8, TNF‐α and VEGF secretion by human keratinocyte was analysed.
Results
Serum IL‐33 levels in patients with PV, PsA and PP were significantly higher than those in healthy controls. Serum IL‐33 levels correlated with serum TNF‐α levels in patients with psoriasis, and decreased after anti‐TNF‐α therapy. IL‐33 stimulated IL‐6 and IL‐8 secretion by human keratinocytes.
Conclusions
These results suggest that serum IL‐33 levels generally reflect increased inflammation in patients with psoriasis.
Japanese Hayabusa2 spacecraft has successfully carried out an impact experiment using a small carry-on impactor (SCI) on an asteroid (162173) Ryugu. We examine the size distribution of particles ...inside and outside an artificial impact crater (the SCI crater) based on the images taken by the optical navigation camera onboard the Hayabusa2 spacecraft. The circumferential variation in particle size distribution inside the SCI crater is recognized and we interpret that major circumferential variation is caused by the large boulders inside the SCI crater that existed prior to the impact. The size distribution inside the SCI crater also shows that the subsurface layer beneath the SCI impact site had a large number of particles with a characteristic size of – 9 cm, which is consistent with the previous evaluations. On the other hand, the size distribution outside the SCI crater exhibits the radial variation, implying that the deposition of ejecta from the SCI crater is involved. The slope of the size distribution outside the crater at small sizes differs from the slope of the size distribution on the surface of Ryugu by approximately 1 or slightly less. This is consistent with the claim that some particles are buried in fine particles of the subsurface origin included in ejecta from the SCI crater. Thus, the particle size distributions inside and outside the SCI crater reveal that the subsurface layer beneath the SCI impact site is rich in fine particles with – 9 cm in size while the particles on the surface have a size distribution of a power-law form with shallower slopes at small sizes due to the deposition of fine ejecta from the subsurface layer. Finally, we discuss a process responsible for this difference in particle size distribution between the surface and the subsurface layers. The occurrence of segregation in the gravitational flow of particles on the surface of Ryugu is plausible.
Graphical Abstract
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