Colorectal cancer (CRC) is a disease in which pathogenesis is influenced by genetic and epigenetic events that occur with tumor initiation and progression. Large variation exists in individual ...patient prognosis and response to chemotherapy, caused by molecular heterogeneity. Certain biomarkers have been identified that can predict clinical outcome beyond tumor staging, and inform treatment selection. Molecular testing is routinely performed in clinical practice for the selection of patients for targeted biological agents or immunotherapy, and is advocated for prognostic stratification. Estimating prognosis can avoid undertreatment or overtreatment and also guide the intensity of patient follow-up. Classifiers of CRC have been developed that integrate genetic and/or epigenetic features. The mutational status of KRAS and BRAF(V600E) oncogenes combined with analysis of the DNA mismatch repair system with/without the CpG island methylator phenotype (CIMP) has been shown to identify colon cancer subtypes with distinct clinical features and prognoses. Gene expression profiling has also been used to subtype CRCs and can overcome the limitations of single/limited gene testing. A recent effort identified 4 consensus molecular subtypes of biological relevance that were associated with different patient outcomes. Efforts to validate and refine these subtypes to include additional genomic features are ongoing. The focus of this article is to highlight molecular markers that can inform clinical decision-making in patients with CRC.
Localized surface plasmon resonance (LSPR) was performed in the deep ultraviolet (UVC) region with Al nanohemisphere structures fabricated by means of a simple method using a combination of vapor ...deposition, sputtering, and thermal annealing without top-down nanofabrication technology such as electron beam lithography. The LSPR in the UV region was obtained and tuned by the initial metal film thickness, annealing temperature, and dielectric spacer layer thickness. Moreover, we achieved a flexible tuning of the LSPR in a much deeper UVC region below 200 nm using a nanohemisphere on a mirror (NHoM) structure. NHoM is a structure in which a metal nanohemisphere is formed on a metal substrate that is interposed with an Al
O
thin film layer. In the experimental validation, Al and Ga were used for the metal hemispheres. The LSPR spectrum of the NHoM structures was split into two peaks, and the peak intensities were enhanced and sharpened. The shorter branch of the LSPR peak appeared in the UVC region below 200 nm. Both the peak intensities and linewidth were flexibly tuned by the spacer thickness. This structure can contribute to new developments in the field of deep UV plasmonics.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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•A brief history and underlying mechanism of the surface-plasmon (SP)-enhanced light emissions were presented.•Enhancements of the spontaneous emission rates of the excited states ...were discussed by the terms of the coupling states between an exciton and SP.•Recent progress and current problems regarding device applications of plasmonic light-emitting diodes (LEDs) were reviewed.•Future possibilities of SP-enhanced light emissions were discussed to extend the wavelength regions from deep ultraviolet (UV) to infrared (IR).
Coupling between surface plasmons (SPs) and excitons can be used to enhance the emission efficiencies of light-emitting materials and devices. This approach had been theoretically predicted and, in 2004, was experimentally demonstrated by our group for enhancing the visible emission from InGaN/GaN quantum wells (QWs). Exciton–SP coupling increases the spontaneous emission rates of the excited states, causes a relative reduction in nonradiative relaxation, and ultimately increases the internal quantum efficiencies (IQEs) of such devices. Here, we present a brief history of the increases in emission efficiency that have been achieved and the underlying mechanism thereof. This method has the potential to enable the development of high-efficiency light-emitting diodes (LEDs), eventually leading to the replacement of fluorescent lights with solid-state light sources. After the initial discovery of this phenomenon, many device structures were proposed and reported; however, their emission efficiencies have thus far remained insufficient for practical application. Here, we also present recent progress on device applications and the current problems that must be solved. Finally, we explain the future possibilities regarding the extension of SP-enhanced light emission over a broader wavelength region, from the deep ultraviolet (UV) to the infrared (IR).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: (1) interrupted ...Pummerer reaction of ketene dithioacetal monoxides with polyfluorophenols followed by 3,3 sigmatropic rearrangement, (2) Zn‐mediated smooth reductive removal of fluoride from the dearomatized intermediate, and (3) acid‐promoted cyclization/aromatization. Mechanistic investigations revealed important characteristic reactivity of polyfluorophenols in the present system. Some of the fluorinated benzofuran products were transformed by utilizing the 2‐methylsulfanyl moieties.
Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: interrupted Pummerer reaction followed by 3,3 sigmatropic rearrangement, Zn‐mediated smooth reductive removal of fluoride from the dearomatized intermediate, and acid‐promoted cyclization/aromatization.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Although serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, the carcinogenic mechanisms remain unknown. We investigated clinicopathological ...characteristics and genetic abnormalities in colorectal polyps and CRC to elucidate carcinogenic mechanisms in SPS.
Methods
We retrospectively analyzed clinicopathological features of colorectal polyps in 44 SPS patients, and examined mutations of genes including APC, RAS, BRAF, and TP53, and microsatellite instability (MSI) in CRC tissues.
Results
Of the 44 patients, 25 (56%) fulfilled WHO criterion 1, 11 (25%) fulfilled criterion 2, and 8 (18%) fulfilled both. A total of 956 polyps were observed; 642 (67%) hyperplastic polyps (HP), 204 (21%) sessile serrated lesions (SSL), 10 (1%) traditional serrated adenoma (TSA), and 100 (11%) adenomas. The median numbers of polyps (/patient) were 10.5 (IQR 2.75–23) HPs, 4.0 (2.0–6.0) SSLs, 0 (0–0) TSA, and 1 (0–3.3) adenoma. SSL and HP located preferentially in the proximal and distal colon, respectively. Twenty-two CRCs were found in 18 patients. Based on the histological coexistence of SSL/TSA, BRAF mutation and MSI, 5 CRCs (26%) were classified as serrated-neoplasia pathway. Conversely, based on the coexistence of adenoma, APC/RAS and TP53 mutations, 11 CRCs (58%) were classified as adenoma–carcinoma pathway. The remaining three were unclassifiable. Most CRCs through adenoma–carcinoma pathway were located in the left-side colorectum and patients bearing those met criterion 2, characterized by many HP and advanced adenomas. Adenoma was a significant risk factor for CRC.
Conclusions
Our results suggest that more than half of the CRCs, particularly those in the left-side colorectum, developed through the adenoma–carcinoma pathway in SPS patients. Adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Treatment of aryl sulfoxides and sulfonanilides with trifluoroacetic anhydride resulted in the dehydrative metal-free construction of the corresponding unsymmetrical biaryls. The reaction would ...proceed via (1) the activation of aryl sulfoxide with the anhydride, (2) interrupted Pummerer reaction of the resulting arylsulfonium with sulfonanilide, (3) 3,3 sigmatropic rearrangement to cleave the transient S–N bond and to form the prospective biaryl C–C bond, and (4) global aromatization. The choice of the amino protecting group is crucial, and only N-sulfonylanilines, i.e., sulfonanilides, could participate in the formation of biaryls.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We semiquantitatively compared the frequency and severity of cerebral amyloid angiopathy (CAA) in the cerebellum and CAA‐positive occipital lobe of 60 subjects from routine autopsies. In the 60 ...subjects with a CAA‐positive occipital lobe, cerebellar CAA was observed in 29 subjects (48.3%), and the severity of cerebellar CAA was relatively mild compared with occipital lobe CAA. Capillary CAA was observed in the occipital lobe of 12 subjects and the cerebellum of three subjects. CAA‐related vasculopathies were observed in the occipital lobe of 15 subjects and the cerebellum of two subjects. The severity of CAA‐related vasculopathy was mild in both of these subjects. Amyloid‐β plaques were observed in the occipital lobe of 54 subjects (90%) and the cerebellum of 16 subjects (26.7%). The severity of amyloid‐β plaques in the cerebellum was mild compared with the occipital lobe. In summary, we confirmed that cerebellar CAA is frequently observed in the cerebellum but with a lower severity than CAA in the occipital lobe.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Anti-EGFR mAb is reported to induce EGFR internalization in colorectal cancer cells. However, the biological relevance of EGFR internalization with anti-EGFR mAb is unknown. Therefore, the relevance ...of EGFR downregulation with anti-EGFR mAb to antitumor activity in colorectal cancer cells was investigated. Quantification of EGFR on the cell surface before cetuximab treatment was assessed by flow cytometry, and its growth-inhibitory effects were measured by Trypan blue exclusion, in 10
wild-type colorectal cancer cell lines, but there was no significant correlation between EGFR number and its growth-inhibitory effect. However, a significant correlation existed between the percentage decrease in the number of EGFRs after cetuximab treatment and its growth-inhibitory effect in those cell lines. Treatment with TGFα, a ligand for EGFR, induced EGFR internalization in colorectal cancer cells, but most EGFRs subsequently recycled to the cell surface, consistent with previous studies. While cetuximab treatment induced EGFR internalization, most receptors subsequently translocated into the late endosome, leading to lysosomal degradation, as revealed by immunoblotting and double immunofluorescence. Cetuximab-sensitive colorectal cancer cells showed greater EGFR internalization, stronger cell growth inhibition, and more augmented apoptotic signals than nonsensitive cells. IHC for EGFR, performed using an EGFR pharmDx Kit (mouse anti-human EGFR mAb clone 2-18C9), in clinical specimens before and after anti-EGFR mAb therapy in 13 colorectal cancer patients showed a significant correlation between the response to anti-EGFR mAb and decreased staining after therapy.
This report clearly demonstrates that anti-EGFR mAb facilitates internalization and subsequent degradation of EGFRs in lysosomes, which is an important determinant of the efficacy of anti-EGFR mAb treatment for colorectal cancer.
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Lead phthalocyanine (PbPc) is well known to be used as a good near-infrared (NIR) light absorber for organic solar cells (OSCs) and photodetectors. The monoclinic and triclinic phases have been ...understood to absorb the visible and NIR regions, respectively, so far. In the present study, we demonstrated from the absorption spectra and theoretical analysis that the visible band considerably originates from not only the monoclinic but also the amorphous and triclinic phases, and revealed the exciton dynamics in the PbPc film from static/time-resolved photoluminescence (PL), which are first reported. By comparing the external quantum efficiency between PbPc- and ZnPc-based OSCs in relation to their structure, morphology, and optical (absorption and PL) characteristics, we unraveled the reasons behind the PbPc film used as a good absorber for NIR-sensitive devices.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK