Pleomorphic dermal sarcoma (PDS) is one of the most common sarcoma of the skin. Currently, limited treatment options exist for advanced stages of the disease. While immune checkpoint inhibitors ...(CPIs) have revolutionized cancer treatment options-their efficacy in PDS has not been explored yet. Here, we present two advanced PDS cases that showed response to anti-PD-1 therapy. Patient A had a locally metastasized PDS and reached a complete remission of the disease after eight cycles of Pembrolizumab. Patient B developed an inoperable relapse of PDS with a complete remission of the disease 4 months after treatment with Pembrolizumab in combination with radiotherapy. To our knowledge, this is the first report of two individuals with advanced PDS that successfully underwent anti-PD1 treatment. By comparing the immune micromilieu to a previously published cohort, we show that the two cases are representative for PDS tumors - potentially making these results more generalizable.
ABSTRACT
In this study we define a new sample of distant powerful radio galaxies in order to study their host galaxy properties and provide targets for future observations of H i absorption with new ...radio telescopes and to understand the fuelling and feedback from such sources. We have cross-matched the Sydney University Molonglo Sky Survey (SUMSS) radio catalogue at 843 MHz with the VISTA Hemisphere Survey (VHS) near-infrared catalogue using the likelihood ratio technique. Photometric redshifts from the Dark Energy Survey are then used to assign redshifts to the radio source counterparts. We found a total of 249 radio sources with photometric redshifts over a 148 deg2 region. By fitting the optical and near-infrared photometry with spectral synthesis models we determine the stellar mass and star formation rates of the radio sources, finding typical stellar masses of 1011–1012 M⊙ for the powerful high-redshift radio galaxies. We also find a population of low-mass blue galaxies. However, by comparing the derived star formation rates to the radio luminosity, we suggest that these sources are false positives in our likelihood ratio analysis. Follow-up, higher resolution (≲5 arcsec) radio imaging would help alleviate these mid-identifications, as the limiting factor in our cross-identifications is the low resolution (∼45 arcsec) of the SUMSS radio imaging.
A system is presented that is capable of measuring subnanosecond reverse recovery times of diodes in wide-bandgap materials over a wide range of forward biases (0 - 1 A) and reverse voltages (0 - 10 ...kV). The system utilizes the step recovery technique and comprises a cable pulser based on a silicon (Si) Photoconductive Semiconductor Switch (PCSS) triggered with an Ultrashort Pulse Laser, a pulse charging circuit, a diode biasing circuit, and resistive and capacitive voltage monitors. The PCSS-based cable pulser transmits a 130 ps rise time pulse down a transmission line to a capacitively coupled diode, which acts as the terminating element of the transmission line. The temporal nature of the pulse reflected by the diode provides the reverse recovery characteristics of the diode, measured with a high bandwidth capacitive probe integrated into the cable pulser. This system was used to measure the reverse recovery times (including the creation and charging of the depletion region) for two Avogy gallium nitride diodes; the initial reverse recovery time was found to be 4 ns and varied minimally over reverse biases of 50-100 V and forward current of 1-100 mA.
Šandalja I palaeocave (“fossil” cave), situated in the southern part of the Istrian peninsula (Croatia), is a well-known locality due to the abundant fossil remains extracted from the bone breccia. ...It is broadly accepted that the fauna is Middle Villafranchian in age. Since the beginning, the taxonomic status of bear remains has caused controversy and, as a consequence, different authors listed between one to three bear species from this site. Detailed revision of dental material confirmed the presence of two bear species –
and
. On the other hand, the previously reported presence of
was refuted. Subsequently, based on the presence of these two bear taxa, the age of the whole faunal assemblage was re-evaluated and determined as Middle Pleistocene (Toringian).
Cutaneous malignant melanoma is an aggressive disease of poor prognosis. Clinical and experimental studies have provided major insight into the pathogenesis of the disease, including the functional ...interaction between melanoma cells and surrounding keratinocytes, fibroblasts, and immune cells. Nevertheless, patients with metastasized melanoma have a very poor prognosis and are largely refractory to clinical therapies. Hence, diagnostic tools to monitor melanoma development, as well as therapeutic targets, are urgently needed. We investigated the expression pattern of the kallikrein-related peptidase 6 (KLK6) in human melanoma tissue sections throughout tumor development. Although KLK6 was not detectable in tumor cells, we found strong KLK6 protein expression in keratinocytes and stromal cells located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions, suggesting a paracrine function of extracellular KLK6 during neoplastic transformation and malignant progression. Accordingly, recombinant Klk6 protein significantly induced melanoma cell migration and invasion accompanied by an accelerated intracellular Ca2+ flux. We could further demonstrate that KLK6-induced intracellular Ca2+ flux and tumor cell invasion critically depends on the protease-activated receptor 1 (PAR1). Our data provide experimental evidence that specific inhibition of the KLK6–PAR1 axis may interfere with the deleterious effect of tumor–microenvironment interaction and represent a potential option for translational melanoma research.
Elevated expression of the X‐linked inhibitor of apoptosis protein (XIAP) has been frequently reported in malignant melanoma suggesting that XIAP renders apoptosis resistance and thereby supports ...melanoma progression. Independent of its anti‐apoptotic function, XIAP mediates cellular inflammatory signalling and promotes immunity against bacterial infection. The pro‐inflammatory function of XIAP has not yet been considered in cancer. By providing detailed in vitro analyses, utilising two independent mouse melanoma models and including human melanoma samples, we show here that XIAP is an important mediator of melanoma neutrophil infiltration. Neutrophils represent a major driver of melanoma progression and are increasingly considered as a valuable therapeutic target in solid cancer. Our data reveal that XIAP ubiquitylates RIPK2, involve TAB1/RIPK2 complex and induce the transcriptional up‐regulation and secretion of chemokines such as IL8, that are responsible for intra‐tumour neutrophil accumulation. Alteration of the XIAP‐RIPK2‐TAB1 inflammatory axis or the depletion of neutrophils in mice reduced melanoma growth. Our data shed new light on how XIAP contributes to tumour growth and provides important insights for novel XIAP targeting strategies in cancer.
SYNOPSIS
XIAP controls melanoma growth without interfering with apoptotic signalling. XIAP induces RIPK2‐mediated inflammatory signalling which provokes neutrophil infiltration and supports tumour progression.
XIAP promotes melanoma growth in two independent mouse melanoma models.
XIAP ubiquitylates RIPK2 in melanoma and mediates IL8 production.
XIAP‐mediated IL8 secretion induces neutrophil recruitment and supports melanoma growth.
XIAP controls melanoma growth without interfering with apoptotic signalling. XIAP induces RIPK2‐mediated inflammatory signalling which provokes neutrophil infiltration and supports tumour progression.
Purpose
To assess whether the neuromuscular activation pattern following Achilles tendon rupture and repair may contributes to the observable functional deficits in this severe and increasingly ...frequent injury.
Methods
In this study, the neuromuscular activation using surface EMG of
n
= 52 patients was assessed during a battery of functional performance tasks to assess potential alterations of muscular activation and recruitment. We analyzed the injured leg vs. the contralateral healthy leg at a mean of 3.5 years following open surgical repair. The testing battery included isokinetic strength testing, bipedal and single-legged heel-rise testing as well as gait analysis.
Results
During isokinetic testing, we observed a higher activation integral for all triceps surae muscles of the injured side during active dorsiflexion, e.g., eccentric loading on the injured leg, while concentric plantarflexion showed no significant difference. Dynamic heel-rise testing showed a higher activation in concentric and eccentric loading for all posterior muscles on the injured side (not significant); while static heel-rise for 10 sec. revealed a significantly higher activation. Further analysis of frequency of fast Fourier-transformed EMG revealed a significantly higher median frequency in the injured leg. Gait analysis revealed a higher pre-activation of the tibialis anterior before ground contact, while medial and lateral gastrocnemius muscles of the injured leg showed a significantly higher activation during push-off phase.
Conclusions
The results of this study provide evidence on the neuromuscular changes 3.5 years following open surgical Achilles tendon repair. These complex neuromuscular changes are manifested to produce the maximum force output whilst protecting the previously injured tendon. The observed alterations may be related to an increased recruitment of type II muscle fibers which could make the muscles prone to fatigue.
Level of evidence
III.
The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a ...large cohort of patients who developed MDS after ABMT for NHL.
Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies. MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias.
Forty-one patients developed MDS at a median of 47 months after ABMT. The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau. Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P =.0003). Karyotypes were performed on bone marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The International Prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment for MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months.
Long-term follow-up demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder.
Fusarium head blight (FHB), caused by Fusarium graminearum, is an important wheat disease that affects grain yield and conformation, and contaminates grains with mycotoxins, including the ...trichothecene deoxynivalenol (DON). The impacts of Fusarium infections on grain filling, grain deformation and rheological properties were assessed under different environmental conditions. Genotypes with elevated grain anthocyanin content were used. Resistance of seven wheat varieties and breeding lines was assessed with artificial infections in the field. Grains from infected and control plots were assessed for proportion of Fusarium damaged kernels, grain filling (thousand kernel weight) and DON accumulation. Biochemical and rheological properties of harvested grain were also assessed. Grain resistance to Fusarium has several components, including resistance against DON accumulation, deformation and stability of grain filling. These mechanisms are interdependent but act independently. Resistance against DON contamination was highly influenced by environmental conditions, but environment had little effect on the other resistance components. Anthocyanins and protein concentrations were unchanged in infected grains, suggesting that FHB does not affect grain biosynthesis processes but impacts the transport of assimilates caused by changes in grain composition. We suggest mat this is the reason for the alterations of rheological properties. The greater the grain resistance, the less was the impact on dough properties. This study suggests that the resilience of rheological properties under FHB infection pressure is an additional component of grain resistance to the disease.
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