Background
Metastatic nodules in perigastric adipose tissue without evidence of lymph node tissue have been reported in gastric cancers. However, the morphological features and clinical significance ...of perigastric tumor deposits (TD) have not been clarified in gastric cancers.
Methods
To demonstrate the clinical implication of perigastric TD, 653 consecutive gastric cancer patients were enrolled and all of their slides were reviewed. Separate tumor nodules in the perigastric fat were classified as perigastric TD and correlated with clinicopathologic features and patient survival.
Results
Perigastric TD were observed in 156 (23.9 %) of 653 patients. Perigastric TD were associated with synchronous distant metastasis (
p
< 0.001), independently of depth and venous invasion. There was a significant difference between the overall survival of those with and without TD by univariate (
p
< 0.001) and multivariate (
p
= 0.001) survival analyses. However, distant metastasis or patient prognosis could not be predicted by the morphologic patterns of the TD (
p
> 0.05). When TD without lymph node tissue and lymph node metastasis were recorded separately, TD were observed in 13 node-negative patients. The overall survival of node-negative patients with TD was significantly worse than that of node-negative patients without TD (
p
< 0.001).
Conclusions
Perigastric TD significantly correlated with distant metastasis and satisfactorily predicted patient outcomes independently of invasion depth, lymph node metastasis, and other clinicopathologic factors. Our findings suggest that perigastric TD should be included in the staging of patients with gastric cancer.
Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of ...AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
Impaired revascularization of transplanted islets is a critical problem that leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are known to aid neovascularization, we aimed ...to enhance islet engraftment by cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or without (islet-only group) human cord blood-derived EPCs, were transplanted into diabetic nude mice. The islet-EPC group reached euglycemia by ∼11 days posttransplantation, whereas the islet-only group did not. Also, the islet-EPC group had a higher serum porcine insulin level than the islet-only group. Islets from the islet-EPC group were more rapidly revascularized at the early period of transplantation without increment of final capillary density at the fully revascularized graft. Enhanced revascularization rate in the islet-EPC group was mainly attributed to stimulating vascular endothelial growth factor-A production from the graft. The rapid revascularization by EPC cotransplantation led to better graft perfusion and recovery from hypoxia. EPC cotransplantation was also associated with greater β-cell proliferation, probably by more basement membrane production and hepatocyte growth factor secretion. In conclusion, cotransplantation of EPCs and islets induces better islet engraftment by enhancing the rate of graft revascularization. These findings might provide a directly applicable tool to enhance the efficacy of islet transplantation in clinical practice.
In this study, we investigated bonding mechanism of a metal foil with glass substrate. We used glass powder to enhance surface area and promote diffusion in the interface. The metal/glass ...powder/glass assembly was annealed at 600 °C for 1 h and adhesion process was monitored. Using transmission electron microscope, element mapping, Raman and energy dispersive X-ray spectroscopy analyses we traced elements’ migration and estimated bonding mechanism.
Cross-diffusion of atoms/ions from metal to glass and in the reverse direction occurred. We estimated that diffusion of iron cations toward the glass substrates induced crystallization of the glass and dendritic crystals were formed.
•Flexible metallic thin foil (invar) is temporary rigidified using glass substrate.•Invar foil – glass assembly is heat treated at 600 °C which results in cross-diffusion of elements.•Metal surface was oxidized forming Fe2+/Fe3+ ions containing mixed oxide.•Diffusion of Fen+ ions from oxide layer toward glass substrate leads to crystallization of glass mass.•Crystallization of glass takes place along Fen+ ions diffusion pathway forming dendritic structure.
This study aimed to investigate the performance of a deep learning-based survival-prediction model, which predicts the overall survival (OS) time of glioblastoma patients who have received surgery ...followed by concurrent chemoradiotherapy (CCRT). The medical records of glioblastoma patients who had received surgery and CCRT between January 2011 and December 2017 were retrospectively reviewed. Based on our inclusion criteria, 118 patients were selected and semi-randomly allocated to training and test datasets (3:1 ratio, respectively). A convolutional neural network–based deep learning model was trained with magnetic resonance imaging (MRI) data and clinical profiles to predict OS. The MRI was reconstructed by using four pulse sequences (22 slices) and nine images were selected based on the longest slice of glioblastoma by a physician for each pulse sequence. The clinical profiles consist of personal, genetic, and treatment factors. The concordance index (C-index) and integrated area under the curve (iAUC) of the time-dependent area-under-the-curve curves of each model were calculated to evaluate the performance of the survival-prediction models. The model that incorporated clinical and radiomic features showed a higher C-index (0.768 (95% confidence interval (CI): 0.759, 0.776)) and iAUC (0.790 (95% CI: 0.783, 0.797)) than the model using clinical features alone (C-index = 0.693 (95% CI: 0.685, 0.701); iAUC = 0.723 (95% CI: 0.716, 0.731)) and the model using radiomic features alone (C-index = 0.590 (95% CI: 0.579, 0.600); iAUC = 0.614 (95% CI: 0.607, 0.621)). These improvements to the C-indexes and iAUCs were validated using the 1000-times bootstrapping method; all were statistically significant (p < 0.001). This study suggests the synergistic benefits of using both clinical and radiomic parameters. Furthermore, it indicates the potential of multi-parametric deep learning models for the survival prediction of glioblastoma patients.
Cancer cachexia is a syndrome accompanying weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer. Since interleukin-6 (IL-6) is one of core mediators ...causing cancer cachexia and kimchi can modulate IL-6 response, we hypothesized dietary intake of kimchi can ameliorate cancer cachexia. In this study, we studied preemptive administration of kimchi can ameliorate mouse colon carcinoma cells colon (C26) adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms of kimchi focused on the changes of muscle atrophy, cachexic inflammation, and catabolic catastrophe. As results, dietary intake of kimchi significantly attenuated the development of cancer cachexia, presented with lesser weight loss, higher muscle preservation as well as higher survival from cancer cachexia in mice. Starting from significant inhibition of IL-6 and its signaling, kimchi afforded significant inhibition of muscle specific ubiquitin-proteasome system including inhibition of atrogin-1 and muscle ring finger protein-1 (MuRF-1) with other muscle related genes including mitofusin-2 (Mfn-2) and PGC-1α. Significant inhibition of lipolysis gene such as adipose triglyceride lipase (ATGL) and hormone-sensitive ligase (HSL) accompanied with significant induction of fatty acid synthase (FAS) and sterol response element binding protein 1 (SREBP1) was achieved with kimchi. As gene regulation, IL-6 and their receptor as well as Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were significantly attenuated with kimchi. In conclusion, dietary intake of cancer preventive kimchi can be an anticipating option to ameliorate cancer cachexia via suppressive action of IL-6 accompanied with decreased muscle atrophy and lipolysis.
PurposeTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with ...this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. MethodsFirst, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. ResultsThe expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. ConclusionFRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.
III-nitride semiconductor-based light-emitting diodes (LEDs) have superior physical properties
such as high thermal stability and brightness, for application to solid-state lighting sources. With the ...commercialization of GaN-based LEDs, improving LED reliability is important because they can be affected by electrostatic discharge, reverse leakage, and breakdown. However, research on the reverse bias characteristics of GaN-based LEDs is insufficient. We studied the reverse breakdown mechanism and demonstrated that a local breakdown can form a conductive channel in GaN-based LEDs, which can be expanded to a novel planar-type LED structure without an n-contact electrode. Furthermore, we found that this approach can be applied to AC-controllable light-emitting devices without any AC-DC converter.
Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis ...related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.
Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic ...strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs).
Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs.
At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower.
This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.