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1.
Nanoscale Horiz ; 7(9): 1054-1064, 2022 08 22.
Article in English | MEDLINE | ID: mdl-35775456

ABSTRACT

A great number of butterfly species in the warmer climate have evolved to exhibit fascinating optical properties on their wing scales which can both regulate the wing temperature and exhibit structural coloring in order to increase their chances of survival. In particular, the Archaeoprepona demophon dorsal wing demonstrates notable radiative cooling performance and iridescent colors based on the nanostructure of the wing scale that can be characterized by the nanoporous matrix with the periodic nanograting structure on the top matrix surface. Inspired by the natural species, we demonstrate a multifunctional biomimetic film that reconstructs the nanostructure of the Archaeoprepona demophon wing scales to replicate the radiative cooling and structural coloring functionalities. We resorted to the SiO2 sacrificial template-based solution process to mimic the random porous structure and laser-interference lithography to reproduce the nanograting architecture of the butterfly wing scale. As a result, the biomimetic structure of the nanograted surface on top of the porous film demonstrated desirable heat transfer and optical properties for outstanding radiative cooling performance and iridescent structural coloring. In this regard, the film is capable of inducing the maximum temperature drop of 8.45 °C, and the color gamut of the biomimetic film can cover 91.8% of the standardized color profile (sRGB).


Subject(s)
Butterflies , Nanostructures , Animals , Biomimetics , Butterflies/physiology , Nanostructures/chemistry , Silicon Dioxide , Wings, Animal/chemistry , Wings, Animal/physiology
2.
ACS Appl Mater Interfaces ; 14(26): 30315-30323, 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35732013

ABSTRACT

Plasmonic color printing has received significant attention owing to its advantages such as nonfading and nontoxic color expression, without necessitating the use of chemical dyes. Recently, color generation from laser-induced plasmonic nanostructures has been extensively explored because of its simplicity, cost-effectiveness, and large-scale processability. However, these methods usually utilize a top-down method that causes unexpected background colors. Here, we proposed a novel method of plasmonic color printing via a bottom-up type laser-induced photomodification process. In the proposed method, selective silver nanoparticles (Ag NPs) structure could be fabricated on a transparent substrate through a unique organometallic solution-based laser patterning process. A set of color palettes was formed on the basis of different processing parameters such as laser fluence, scanning speed, and baking time. This color change was verified by finite-difference time-domain (FDTD) simulations via monitoring the spectral peak shift of the localized surface plasmon resonance (LSPR) at Ag NPs. It was also confirmed that the colors can be fabricated at a relatively high scanning speed (≥10 mm/s) on a large substrate (>300 mm2). Since semitransparent color images can be patterned on various transparent substrates, this process will broaden the application range of laser-induced plasmonic color generation.

3.
Small Methods ; 6(5): e2200150, 2022 May.
Article in English | MEDLINE | ID: mdl-35388984

ABSTRACT

Metal microhoneycomb structures have received considerable attention as a type of interaction-efficient functional devices owing to their unique morphology and material properties. Microhoneycomb structures are mainly fabricated using the well-known breath-figure method. However, additional post-treatments are required to produce a metal structure because it is a polymer-based process, and this necessitates expensive, complex, and multi-step fabrication processes. Therefore, a simple, low-cost metal honeycomb fabrication process is necessary. In this paper, the laser patterning of an organometallic solution to produce silver microhoneycomb (Ag microhoneycomb) structures is proposed. Various phenomena such as rapid organic evaporation, silver nanoparticle solidification, and material reorganization from Marangoni flow are found to enable patterning-induced microhoneycomb formation. Parametric studies demonstrate that the pore size can be easily controlled through simple laser parameter changes. In addition, cyclic voltammetry and electrochemical impedance spectroscopy studies confirm the potential electrochemical applications of the Ag microhoneycomb structures based on the variation of electrochemical redox behavior depending on the pore size. Owing to the excellent advantages of one-step laser patterning without any templates, the proposed process will likely promote the practical use of the metal microhoneycomb structures.

4.
Materials (Basel) ; 14(11)2021 May 26.
Article in English | MEDLINE | ID: mdl-34073429

ABSTRACT

Magnesium-based alloys are attractive as hydrogen storage materials due to their lightweight and high absorption, but their high operating temperatures and very slow kinetics are obstacles to practical applications. Therefore, the effect of CaO has improved the hydrogenation kinetics and slowed down the degradation. The Mg2NiHx-CaO composites were prepared by hydrogen-induced mechanical alloying (HIMA). Hydrogenation kinetics was performed by using an Automatic PCT Measuring System and evaluated in the temperature range of 423, 523, and 623 K. As a result of calculating the hydrogen absorption amounts through the hydrogenation kinetics curve, they were calculated as about 0.52 wt%, 1.21 wt%, and 1.59 wt% (Mg2NiHx-10 wt% CaO). In this study, the material environmental aspects of Mg2NiHx-CaO composites were investigated through life cycle assessment (LCA). LCA was performed analyzing the environmental impact characteristics of the manufacturing process by using Gabi software and the Eco-Indicator 99' and Centrum voor Milieuweten schappen (CML 2001) methodology. As a result, the contents of global warming potential (GWP) and fossil fuels were found to have a higher impact than other impact categories.

5.
Nanotechnology ; 32(31)2021 May 14.
Article in English | MEDLINE | ID: mdl-33892481

ABSTRACT

Designing uniform plasmonic surfaces in a large area is highly recommended for surface-enhanced Raman scattering (SERS). As periodic morphologies exhibit uniform SERS and optical tunability, diverse fabrication methods of periodic nanostructures have been reported for SERS applications. Laser interference lithography (LIL) is one of the most versatile tools since it can rapidly fabricate periodic patterns without the usage of photomasks. Here, we explore complex interference patterns for spatially uniform SERS sensors and its cost-effective fabrication method termed multi-exposure laser interference lithography (MELIL). MELIL can produce nearly periodic profiles along every direction confirmed by mathematical background, and in virtue of periodicity, we show that highly uniform Raman scattering (relative standard deviation <6%) can also be achievable in complex geometries as the conventional hole patterns. We quantitatively characterize the Raman enhancement of the MELIL complex patterns after two different metal deposition processes, Au e-beam evaporation and Ag electroplating, which results in 0.387 × 105and 1.451 × 105in enhancement factor respectively. This alternative, vacuum-free electroplating method realizes an even more cost-effective process with enhanced performance. We further conduct the optical simulation for MELIL complex patterns which exhibits the broadened and shifted absorption peaks. This result supports the potential of the expanded optical tunability of the suggested process.

6.
Sci Rep ; 11(1): 2262, 2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33500481

ABSTRACT

As silver nanowires (Ag NWs) are usually manufactured by chemical synthesis, a patterning process is needed to use them as functional devices. Pulsed laser ablation is a promising Ag NW patterning process because it is a simple and inexpensive procedure. However, this process has a disadvantage in that target materials are wasted owing to the subtractive nature of the process involving the removal of unnecessary materials, and large quantities of raw materials are required. In this study, we report a minimum-waste laser patterning process utilizing silver nanoparticle (Ag NP) debris obtained through laser ablation of Ag NWs in liquid media. Since the generated Ag NPs can be used for several applications, wastage of Ag NWs, which is inevitable in conventional laser patterning processes, is dramatically reduced. In addition, electrophoretic deposition of the recycled Ag NPs onto non-ablated Ag NWs allows easy fabrication of junction-enhanced Ag NWs from the deposited Ag NPs. The unique advantage of this method lies in using recycled Ag NPs as building materials, eliminating the additional cost of junction welding Ag NWs. These fabricated Ag NW substrates could be utilized as transparent heaters and stretchable TCEs, thereby validating the effectiveness of the proposed process.

7.
Int J Mol Sci ; 21(22)2020 Nov 16.
Article in English | MEDLINE | ID: mdl-33207653

ABSTRACT

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in 'cold' or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn 'cold' tumors 'hot,' increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.


Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/therapy , Oncolytic Virotherapy , Oncolytic Viruses , Tumor Microenvironment , Clinical Trials as Topic , Humans
8.
J Clin Imaging Sci ; 10: 22, 2020.
Article in English | MEDLINE | ID: mdl-32363084

ABSTRACT

Imaging features of benign mixed Brenner tumor and mucinous cystadenomas are rarely reported. This report aims to describe the case of a benign mixed Brenner tumor and mucinous cystadenoma with a dominant Brenner tumor component and to review the typical imaging features of this ovarian neoplasm.

9.
Sensors (Basel) ; 18(11)2018 Nov 21.
Article in English | MEDLINE | ID: mdl-30469441

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) is a promising analytical tool due to its label-free detection ability and superior sensitivity, which enable the detection of single molecules. Since its sensitivity is highly dependent on localized surface plasmon resonance, various methods have been applied for electric field-enhanced metal nanostructures. Despite the intensive research on practical applications of SERS, fabricating a sensitive and reproducible SERS sensor using a simple and low-cost process remains a challenge. Here, we report a simple strategy to produce a large-scale gold nanoparticle array based on laser interference lithography and the electrophoretic deposition of gold nanoparticles, generated through a pulsed laser ablation in liquid process. The fabricated gold nanoparticle array produced a sensitive, reproducible SERS signal, which allowed Rhodamine 6G to be detected at a concentration as low as 10-8 M, with an enhancement factor of 1.25 × 105. This advantageous fabrication strategy is expected to enable practical SERS applications.

10.
Biomaterials ; 65: 163-74, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26164117

ABSTRACT

Adenovirus (Ad) is a widely used vector for cancer gene therapy but its therapeutic efficacy is limited by low coxsackievirus and adenovirus receptor (CAR) expression in tumors and non-specifically targeted infection. Ad infectivity and specificity can be markedly improved by creating Ad-magnetic nanoparticles cluster complexes and directing their migration with an external magnetic field (MGF). We electrostatically complexed GFP-expressing, replication-incompetent Ad (dAd) with PEGylated and cross-linked iron oxide nanoparticles (PCION), generating dAd-PCION complexes. The dAd-PCION showed increased transduction efficiency, independent of CAR expression, in the absence or presence of an MGF. Cancer cell killing and intracellular oncolytic Ad (HmT)-PCION replication significantly increased with MGF exposure. Site-directed, magnetically-targeted delivery of the HmT-PCION elicited significantly greater therapeutic efficacy versus treatment with naked HmT or HmT-PCION without MGF in CAR-negative MCF7 tumors. Immunohistochemical tumor analysis showed increased oncolytic Ad replication in tumors following infection by HmT-PCION using an MGF. Whole-body bioluminescence imaging of tumor-bearing mice showed a 450-fold increased tumor-to-liver ratio for HmT-PCION with, versus without, MGF. These results demonstrate the feasibility and potential of external MGF-responsive PCION-coated oncolytic Ads as smart hybrid vectors for cancer gene therapy.


Subject(s)
Adenoviridae/chemistry , Ferric Compounds/chemistry , Magnetite Nanoparticles/chemistry , Neoplasms/therapy , Oncolytic Viruses/chemistry , Adenoviridae/genetics , Animals , Cell Line, Tumor , Genetic Therapy , Humans , Magnetic Fields , Mice , Neoplasms/genetics , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Polyethylene Glycols/chemistry , Transduction, Genetic
11.
Int J Cancer ; 137(9): 2253-69, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-25944623

ABSTRACT

Various ways to inhibit vascular endothelial growth factor (VEGF), a key facilitator in tumor angiogenesis, are being developed to treat cancer. The soluble VEGF decoy receptor (FP3), due to its high affinity to VEGF, is a highly effective and promising strategy to disrupt VEGF signaling pathway. Despite potential advantage and potent therapeutic efficacy, its employment has been limited by very poor in vivo pharmacokinetic properties. To address this challenge, we designed a novel oncolytic adenovirus (Ad) expressing FP3 (RdB/FP3). To demonstrate the VEGF-specific nature of RdB/FP3, replication-incompetent Ad expressing FP3 (dE1/FP3) was also generated. dE1/FP3 was highly effective in reducing VEGF expression and functionally elicited an antiangiogeneic effect. Furthermore, RdB/FP3 exhibited a potent antitumor effect compared with RdB or recombinant FP3. Consistent with these data, RdB/FP3 was shown to greatly decrease VEGF expression level and vessel density and increase apoptosis in both tumor endothelial and tumor cells, verifying potent suppressive effects of RdB/FP3 on VEGF-mediated tumor angiogenesis in vivo. Importantly, the therapeutic mechanism of antitumor effect mediated by RdB/FP3 is associated with prolonged VEGF silencing efficacy and enhanced oncolysis via cancer cell-specific replication of oncolytic Ad. Taken together, RdB/FP3 provides a new promising therapeutic approach in the treatment of cancer and angiogenesis-related diseases.


Subject(s)
Adenoviridae/genetics , Oncolytic Virotherapy , Oncolytic Viruses/genetics , Angiogenesis Inhibitors/biosynthesis , Angiogenesis Inhibitors/genetics , Angiogenesis Inhibitors/pharmacology , Animals , Cell Line, Tumor , Cell Movement , Gene Expression , HEK293 Cells , Humans , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic/prevention & control , Rats, Sprague-Dawley , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/genetics
12.
J Control Release ; 205: 134-43, 2015 May 10.
Article in English | MEDLINE | ID: mdl-25575865

ABSTRACT

Although oncolytic adenoviruses (Ads) are an attractive option for cancer gene therapy, the intravenous administration of naked Ad still encounters unfavorable host responses, non-specific interactions, and heterogeneity in targeted cancer cells. To overcome these obstacles and achieve specific targeting of the tumor microenvironment, Ad was coated with the pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine-co-l-phenylalanine) (PEGbPHF). The physicochemical properties of the generated nanocomplex, Ad/PEGbPHF, were assessed. At pH6.4, GFP-expressing Ad/PEGbPHF induced significantly higher GFP expression than naked Ad in both coxsackie and adenovirus receptor (CAR)-positive and -negative cells. To assess the therapeutic efficacy of the Ad/PEGbPHF complex platform, an oncolytic Ad expressing VEGF promoter-targeting transcriptional repressor (KOX) was used to form complexes. At pH6.4, KOX/PEGbPHF significantly suppressed VEGF gene expression, cancer cell migration, vessel sprouting, and cancer cell killing effect compared to naked KOX or KOX/PEGbPHF at pH7.4, demonstrating that KOX/PEGbPHF can overcome the lack of CAR that is frequently observed in tumor tissues. The antitumor activity of KOX/PEGbPHF systemically administered to a tumor xenograft model was significantly higher than that of naked KOX. Furthermore, KOX/PEGbPHF showed lower hepatic toxicity and did not induce an innate immune response against Ad. Altogether, these results demonstrate that pH-sensitive polymer-coated Ad complex significantly increases net positive charge upon exposure to hypoxic tumor microenvironment, allowing passive targeting to the tumor tissue. It may offer superior potential for systemic therapy, due to its improved tumor selectivity, increased therapeutic efficacy, and lower toxicity compared to naked KOX.


Subject(s)
Adenoviridae/pathogenicity , Neoplasms/therapy , Neovascularization, Physiologic , Oncolytic Virotherapy/methods , Oncolytic Viruses/pathogenicity , Tumor Microenvironment , Adenoviridae/genetics , Adenoviridae/immunology , Adenovirus E1A Proteins/genetics , Adenovirus E1B Proteins/genetics , Animals , Cell Hypoxia , Cell Movement , Gene Deletion , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , HEK293 Cells , Histidine/chemistry , Humans , Hydrogen-Ion Concentration , Immunity, Innate , MCF-7 Cells , Mice, Nude , Mutation , Neoplasm Invasiveness , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/virology , Oncolytic Virotherapy/adverse effects , Oncolytic Viruses/genetics , Oncolytic Viruses/immunology , Peptides/chemistry , Polyethylene Glycols/chemistry , Rats, Sprague-Dawley , Time Factors , Tissue Culture Techniques , Transduction, Genetic , Tumor Burden , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor Assays
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 5867-70, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26737626

ABSTRACT

Recording the activity of neural populations at high sampling rates is a fundamental requirement for understanding computation in neural circuits. Two photon microscopy provides one promising approach towards this. However, neural circuits are three dimensional, and functional imaging in two dimensions fails to capture the 3D nature of neural dynamics. Electrically tunable lenses (ETLs) provide a simple and cheap method to extend laser scanning microscopy into the relatively unexploited third dimension. We have therefore incorporated them into our Adaptive Spiral Scanning (SSA) algorithm, which calculates kinematically efficient scanning strategies using radially modulated spiral paths. We characterised the response of the ETL, incorporated its dynamics using MATLAB models of the SSA algorithm and tested the models on populations of Izhikevich neurons of varying size and density. From this, we show that our algorithms can theoretically at least achieve sampling rates of 36.2Hz compared to 21.6Hz previously reported for 3D scanning techniques.


Subject(s)
Photons , Algorithms , Imaging, Three-Dimensional , Microscopy, Confocal , Neurons , Radionuclide Imaging
14.
Biomacromolecules ; 16(1): 87-96, 2015 Jan 12.
Article in English | MEDLINE | ID: mdl-25400213

ABSTRACT

Adenovirus (Ad) vectors show promise as cancer gene therapy delivery vehicles, but immunogenic safety concerns and coxsackie and adenovirus receptor (CAR)-dependency have limited their use. Alternately, biocompatible and bioreducible nonviral vectors, including arginine-grafted cationic polymers, have been shown to deliver nucleic acids through a cell penetration peptide (CPP) and protein transduction domain (PTD) effect. We utilized the advantages of both viral and nonviral vectors to develop a hybrid gene delivery vehicle by coating Ad with mPEG-PEI-g-Arg-S-S-Arg-g-PEI-mPEG (Ad/PPSA). Characterization of Ad/PPSA particle size and zeta potential showed an overall size and cationic charge increase in a polymer concentration-dependent manner. Ad/PPSA also showed a marked transduction efficiency increase in both CAR-negative and -positive cells compared to naked Ad. Competition assays demonstrated that Ad/PPSA produced higher transgene expression levels than naked Ad and achieved CAR-independent transduction. Oncolytic Ad (DWP418)/PPSA was able to overcome the nonspecificity of polymer-only therapies by demonstrating cancer-specific killing effects. Furthermore, the DWP418/PPSA nanocomplex elicited a 2.24-fold greater antitumor efficacy than naked Ad in vivo. This was supported by immunohistochemical confirmation of Ad E1As accumulation in MCF7 xenografted tumors. Lastly, intravenous injection of DWP418/PPSA elicited less innate immune response compared to naked Ad, evaluated by interleukin-6 cytokine release into the serum. The increased antitumor effect and improved vector targeting to both CAR-negative and -positive cells make DWP418/PPSA a promising tool for cancer gene therapy.


Subject(s)
Adenoviridae/chemistry , Antineoplastic Agents/chemistry , Biocompatible Materials/chemistry , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Oncolytic Viruses/chemistry , Polymers/chemistry , Animals , Antineoplastic Agents/administration & dosage , Biocompatible Materials/administration & dosage , Female , HEK293 Cells , Humans , MCF-7 Cells , Mice , Mice, Nude , Oncolytic Virotherapy/methods , Polymers/administration & dosage , Treatment Outcome , Xenograft Model Antitumor Assays/methods
15.
Tuberc Respir Dis (Seoul) ; 76(6): 289-91, 2014 Jun.
Article in English | MEDLINE | ID: mdl-25024723

ABSTRACT

Malignant fibrous histiocytoma (MFH), a type of sarcoma, is a malignant neoplasm with uncertain origins that arise from both the soft tissues and the bone. The occurrence of MFH on the chest wall is extremely rare. We hereby report a case of a 72-year-old woman who was incidentally detected with MFH after a traffic accident.

16.
Tuberc Respir Dis (Seoul) ; 75(2): 59-66, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24023558

ABSTRACT

BACKGROUND: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. METHODS: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. RESULTS: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). CONCLUSION: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

17.
J Cutan Pathol ; 35(10): 955-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18494821

ABSTRACT

Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines.


Subject(s)
Carcinoma, Merkel Cell/pathology , Neoplasms, Complex and Mixed/pathology , Skin Neoplasms/pathology , Aged, 80 and over , Arm/pathology , Carcinoma, Merkel Cell/metabolism , Cell Differentiation , Female , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Neoplasms, Complex and Mixed/metabolism , Skin Neoplasms/metabolism
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