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Background: We evaluated the therapeutic efficacy of GC1118, a novel anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. Methods: This study was a multicenter, open‐label, single‐arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6‐month progression‐free survival rate (PFS6). Next‐generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118. Results: Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%–25.8%, Wilson method). The median progression‐free survival was 1.7 months (range: 28 days–7.2 months) and median overall survival was 5.7 months (range: 2–22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin‐related toxicity. Genomic analysis revealed that the immune‐related signatures were upregulated in patients with tumor regression. Conclusion: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune‐mediated antitumor efficacy of GC1118. [ABSTRACT FROM AUTHOR]

Non‐small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti‐cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM‐NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri‐culture platform is proposed for recapitulating positive feedback from BM‐NSCLC and astrocytes and brain‐specific endothelial cells, two major players in bTME. Advanced imaging and quantitative functional assessment of the 3D tri‐culture model enable real‐time live imaging of cell viability and separate analyses of genomic/molecular/secretome from each subset. Susceptibility of multiple patient‐derived BM‐NSCLCs to representative targeted agents is altered and secretion of serpin E1, interleukin‐8, and secreted phosphoprotein 1, which are associated with tumor aggressiveness and poor clinical outcome, is increased in tri‐culture. Notably, multiple signaling pathways involved in inflammatory responses, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, and cancer metastasis are activated in BM‐NSCLC through interaction with two bTME cell types. This novel platform offers a tool to elucidate potential molecular targets and for effective anti‐cancer therapy targeting the crosstalk between metastatic cancer cells and adjacent components of bTME. [ABSTRACT FROM AUTHOR]

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T‐cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non‐small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T‐cell activities leading to poor clinical outcomes. First, we verified PMN‐MDSCs, monocytic‐MDSCs (M‐MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T‐cell activities and induced T‐cell exhaustion. The analysis of NSCLC patients treated with anti‐PD‐1 immunotherapy demonstrated that low PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most malignant primary brain tumor in adults with substantial genomic alterations. The median survival is approximately 14.6 months, despite aggressive therapeutic intervention, which comprised of surgical resection, radiotherapy, and chemotherapy. Recent studies on cancer genomic have revealed crucial insights into dynamic molecular subgroups within GBM, which govern distinct clinical response and sensitivity of each individual to therapy. In the present study, we analyzed genomic composition of primary GBMs between two ethnic groups [IRCR (Institute of Refractory Cancer Research), and TCGA (The Cancer Genome Atlats)] to explore genomic and molecular features that constitute malignant behavior of glioblastoma based on distinct ethnicity. We identified enrichments of MAPK and p53 pathways in IRCR patients, while aberrant activation of Receptor Tyrosine Kinases (RTKs) were predominant in TCGA cohort. We also discovered differential clinical prognosis between two groups and explored essential features that present such diversity. [ABSTRACT FROM AUTHOR]

Chemical gas sensors have attracted much attention with the purposes of environmental hazardous gas detection and health monitoring via exhaled breath analysis. In particular, semiconducting metal oxide (SMO)‐based chemiresistors have been considered as one of the most attractive sensing platforms owing to its simple operation, low cost, ease of miniaturization and integration to mobile devices. However, SMO‐based sensors suffer from sluggish gas reactions and poor responses. To enhance their sensing characteristics, one‐dimensional (1D) nanostructures with large surface area and high porosity are desired, since sensing reactions with analytes mainly occur at the surface of the sensing layers. In addition, uniform catalyst functionalization on SMO supports is beneficial in terms of gas response, reaction speed, and selectivity. In this review, we comprehensively highlight recent progresses on diverse hollow 1D nanofibrous structures prepared using a well‐reputed technique of electrospinning, and their unique morphological advantages as highly sensitive chemical sensing layers. Finally, future perspectives on the synthesis and sensing characterizations of hollow nanofibrous sensing materials functionalized with robust catalysts are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Glioblastomas are among the most fatal brain tumors. Although no effective treatment option is available for recurrent glioblastomas (GBMs), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor. We retrospectively reviewed patients with recurrent GBM who received bevacizumab to identify biomarkers for predicting clinical response to bevacizumab. Following defined criteria, the patients were categorized into two clinical response groups, and their genetic and transcriptomic results were compared. Angiogenesis‐related gene sets were upregulated in both responders and nonresponders, whereas genes for each corresponding angiogenesis pathway were distinct from one another. Two gene sets were made, namely, the nonresponder angiogenesis gene set (NAG) and responder angiogenesis gene set (RAG), and then implemented in independent GBM cohort to validate our dataset. A similar association between the corresponding gene set and survival was observed. In NAG, COL4A2 was associated with a poor clinical outcome in bevacizumab‐treated patients. This study demonstrates that angiogenesis‐associated gene sets are composed of distinct subsets with diverse biological roles and they represent different clinical responses to anti‐angiogenic therapy. Enrichment of a distinct angiogenesis pathway may serve as a biomarker to predict patients who will derive a clinical benefit from bevacizumab. [ABSTRACT FROM AUTHOR]

Chemical sensors have been essential components in recent years due to the gathering attention in environmental monitoring and healthcare. In this review, the authors comprehensively highlight recent progresses on the 1D chemiresistive-type sensors based on semiconductor metal oxides (SMOs) and optical-type sensors, which are prepared by electrospinning technique. In the part of chemiresistive-type sensors, diverse synthesis techniques for 1D SMO nanofibrous structure are presented with controlled microstructure and surface morphology. In addition, unique functionalization routes of emerging nanocatalysts encapsulated by bio-inspired templates are described for the next generation catalyst on the 1D SMO nanofibers (NFs). For the optical-type sensors, new classes of 1D NFs employing specific absorption and emission properties are introduced. In particular, diverse 1D NF-based colorimetric and fluorescence sensors as well as Raman and surface-enhanced Raman scattering sensors are covered in the view point of material preparation and optical sensing properties. Finally, the authors prospect future research directions to overcome current limitations and challenges to achieve high performance chemical sensors. [ABSTRACT FROM AUTHOR]

Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC. [ABSTRACT FROM AUTHOR]

Background Although much research has been conducted into the origin of syringoma, the histogenesis and differentiation of it remains controversial. The published studies examined various antibodies, and our study is an additional immunohistochemical work-up. Objective We attempted to identify the cell that acts as the precise origin of a syringoma, based on a comparative analysis of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratin (CK) 5 through immunohistochemical staining in the solid strand of basophilic epithelial cells of syringoma. Methods A total of 31 patients with biopsy-confirmed syringoma were included in this study. Each sample was analyzed with antibodies to CEA, EMA, and CK5. These markers were indicating each part of the normal sweat gland structure: CEA stains the luminal surface of sweat ductal structures; EMA stains the peripheral cells of normal dermal ducts and the intraepidermal duct; CK5 stains the outer cells of the dermal duct and lower intraepidermal duct but does not stain the intraepidermal duct located in the upper epidermis. Results We were able to confirm that the solid strands stained for EMA and CK5, as did the outer cells of the ductal structure. However, the solid strands did not stain with CEA. Conclusions The results indicated that solid strands observed in syringomas originate from the outer cells of the two layers of cells that compose the lower epidermal duct or the transitional portion between the intraepidermal duct and dermal duct in the normal eccrine or apocrine structure. Thus, we surmise that a syringoma is developed by the proliferation of these cells. [ABSTRACT FROM AUTHOR]

The article presents case studies of four children with subepidermal calcified nodules found in their sole. It states that the children were brought to the hospital due to solid, yellowish-white nodules similar to rice grains. Based on hispathological findings through von Kossa straining, the nodules found under the epidermis were revealed as calcium characterized by homogenous basophilic substances.

ABSTRACT People with sensitive skin (SS) are those who state their skin is more sensitive than that of average persons. The stratum corneum is responsible for maintaining skin barrier function. Ceramides, major constituents of stratum corneum lipids, have been shown to predominantly contribute to the role. It has been suggested that barrier function in SS is decreased. However, we could find very few reports about stratum corneum ceramides in SS. This study was done to find out differences in stratum corneum ceramides between SS and non-SS groups. Fifty individuals (20 with SS and 30 with non-SS) were recruited. Lactic acid sting test (LAST) was performed on the left cheek. On six sites including the right cheek, arm, thigh, leg, back and palm, transepidermal water loss (TEWL) and erythema index (EI) were measured. On the above six sites, stratum corneum sheets were obtained by stripping with cyanoacrylate resin and stratum corneum lipids were extracted, then, analyzed by high-performance liquid chromatography electrospray ionization mass spectrometry. LAST scores were higher in the SS group, but not statistically significant. There were no differences in TEWL and EI values between the two groups. The mean value of the quantity of stratum corneum ceramides on the face was significantly lower in the SS group. On other sites, mean values were also lower in the SS group, but not statistically significant. The quantity of ceramides was significantly decreased in the face of the SS group compared to that of the non-SS group. These results suggest that the decrease in stratum corneum ceramides on facial skin could be related to SS development. [ABSTRACT FROM AUTHOR]

Metal oxide nanosheets having high mesoporosity, grain size distribution of 5–10 nm, and ultrathin thickness have attracted much attention due to their intriguing properties such as high surface‐to‐volume ratio and superior chemical activities. However, 2D nanostructures tend to restack, inducing a decrease in accessible surface area and a number of pores. To solve this problem, herein, a unique synthetic method of crumpled metal oxide nanosheets using spray pyrolysis of metal ion–coated graphene oxide, followed by heat treatment, is reported. This method is applicable not only to single‐component metal oxides but also to heterogeneous multicomponent metal oxides in which composition can be controlled. Crumpled SnO2, ZnO, and Co3O4 as well as SnO2/ZnO and SnO2/Co3O4 nanosheets with heterogeneous interfaces are successfully synthesized and used as superior gas sensing layers. Because of the abundant reaction sites, well‐developed porosity for high gas accessibility, the formation of heterojunctions, the crumpled SnO2/ZnO and SnO2/Co3O4 nanosheets exhibit outstanding sensing performance (Rair/Rgas = 20.25 toward 5 ppm formaldehyde, and Rair/Rgas = 14.13 toward 5 ppm acetone, respectively). This study can contribute to the realization of a family of heterogeneous crumpled metal oxide nanosheets that can be applied to various research fields. [ABSTRACT FROM AUTHOR]

Front Cover: The feature describes two different types of chemical sensors, i.e., chemiresistive type sensors and optical sensors. For the chemiresistive type sensors, electrical signals are modulated during the reaction with chemical gas species. On the other hand, distinctive color changes are occurred in the case of optical sensors after the reaction with chemical analytes. The feature is designed for the review paper about one‐dimensional nanofibrous sensing structures for chemiresistive type sensors and optical sensors. This is reported by Seon‐Jin Choi, Luana Persano, Andrea Camposeo, Ji‐Soo Jang, Won‐Tae Koo, Sang‐Joon Kim, Hee‐Jin Cho, Il‐Doo Kim and Dario Pisignano, in article number 1600569. [ABSTRACT FROM AUTHOR]