Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta ...1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.
The ear is a common site for keloid formation, usually after trauma or ear piercing. This study is a meta-analysis to identify effective treatments for ear keloids after surgical excision.
A ...systematic literature review and meta-analysis were performed using core databases. Postoperative adjuvant treatment modalities for ear keloids and recurrence rates were extracted and analyzed. Fixed and random effect models were applied.
Twenty-five studies published before August of 2015 were identified. The recurrence rate after surgical excision of an ear keloid in the triamcinolone group was estimated as 15.4 percent (95 percent CI, 9.4 to 24.1 percent; p < 0.001). The recurrence rate in the radiation therapy group was estimated as 14.0 percent (95 percent CI, 9.6 to 19.9 percent; p < 0.001).
Although a large-scale, randomized study is required for confirmation, both triamcinolone and radiation therapy provided outstanding treatment for ear keloids after surgical excision without a significant difference between the two treatments.
Background & Aims: The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy ...can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker. Methods: We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3–4 weeks after metastasectomy and serially, if patients agreed. Results: Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemotherapy. The detection rate of ctDNA was higher in liver metastasis (p = 0.0045) and tumors measuring ≥1 cm (p = 0.0183). ctDNA was less likely to be detected if the response to chemotherapy was good. After metastasectomy, ctDNA was found in 4 (6%) cases with rapid progressive disease. Conclusion: The biological factors affecting the ctDNA shedding from the tumor should be considered when applying ctDNA assays in a clinical setting. After metastasectomy for oligometastatic lesions in good responders of chemotherapy, most ctDNA was cleared or existed below the detection level. To assist clinical decision making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.
Antarctica is considered a relatively uncontaminated region with regard to the infectious diseases because of its extreme environment, and isolated geography. For the genetic characterization and ...molecular epidemiology of the newly found penguin adenovirus in Antarctica, entire genome sequencing and annual survey of penguin adenovirus were conducted. The entire genome sequences of penguin adenoviruses were completed for two Chinstrap penguins (Pygoscelis antarctica) and two Gentoo penguins (Pygoscelis papua). The whole genome lengths and G+C content of penguin adenoviruses were found to be 24,630-24,662 bp and 35.5-35.6%, respectively. Notably, the presence of putative sialidase gene was not identified in penguin adenoviruses by Rapid Amplification of cDNA Ends (RACE-PCR) as well as consensus specific PCR. The penguin adenoviruses were demonstrated to be a new species within the genus Siadenovirus, with a distance of 29.9-39.3% (amino acid, 32.1-47.9%) in DNA polymerase gene, and showed the closest relationship with turkey adenovirus 3 (TAdV-3) in phylogenetic analysis. During the 2008-2013 study period, the penguin adenoviruses were annually detected in 22 of 78 penguins (28.2%), and the molecular epidemiological study of the penguin adenovirus indicates a predominant infection in Chinstrap penguin population (12/30, 40%). Interestingly, the genome of penguin adenovirus could be detected in several internal samples, except the lymph node and brain. In conclusion, an analysis of the entire adenoviral genomes from Antarctic penguins was conducted, and the penguin adenoviruses, containing unique genetic character, were identified as a new species within the genus Siadenovirus. Moreover, it was annually detected in Antarctic penguins, suggesting its circulation within the penguin population.
It has been known that the enantioselectivity of the chiral Lewis base-catalyzed, SiCl4-promoted kinetic resolution of α,β-dichloro cis-vinyl epoxide is highly influenced by the configuration of the ...distal β-chlorine-bearing stereocenter. In this report, the precise nature of this unusual remote stereocontrol was investigated both experimentally and theoretically. Upon examination of a substrate that has an alkyl group in place of the β-chlorine substituent, the spatial location of major catalyst-substrate interaction was determined. Subsequently, through computational analysis of transition states, the steric repulsion by the β-substituents as well as the additional C–H/π hydrogen bond by the alkyl substituent were proposed as the crucial stereo-determining factors.
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•The remote stereocontrol in the kinetic resolution of chlorinated vinyl epoxide was investigated.•The role of the β-chlorine-bearing stereocenter has been elucidated by DFT calculation of transition state.•Non-covalent interactions including C–H/π hydrogen bonding are proposed as key stereodetermining factors.
Non-operative treatment is the mainstay of colonic diverticulitis, but some patients require surgery due to non-operative treatment failure. This study aims to identify risk factors for the failure ...of non-operative treatment of colonic diverticulitis. From January 2011 to December 2020, we retrospectively reviewed 2362 patients with non-operative treatment for first-attack acute diverticulitis. Patients were categorized into non-operative treatment success or failure groups. Clinical characteristics and serum inflammatory markers were analyzed by multivariable logistic regression to determine risk factors for non-operative treatment failure of colonic diverticulitis. Overall, 2.2% (n = 50) of patients underwent delayed surgery within 30 days (median 4.0 3.0; 8.0) due to non-operative treatment failure. Multivariable logistic regression identified that platelet to lymphocyte ratio (odds ratio OR, 4.2; 95% confidence interval CI, 0.05-0.13; p < 0.001), diabetes mellitus (OR, 2.2; 95% CI, 0.01-0.09; p = 0.025), left-sided colonic diverticulitis (OR, 4.1; 95% CI, 0.04-0.13; p < 0.001), and modified Hinchey classification (OR, 6.2; 95% CI, 0.09-0.17; p < 0.001) were risk factors for non-operative treatment failure. Platelet to lymphocyte ratio (PLR) is a potential risk factor for the non-operative treatment failure of acute first-attack colonic diverticulitis. Therefore, patients with higher PLR during non-operative treatment should be monitored with special caution.
Breast cancers that express epidermal growth factor (EGF) receptors (EGFRs) are associated with poor prognosis. Our group recently showed in breast cancer patients that EGFR expression is strongly ...correlated with high tumor uptake of the glucose analogue, 18F-fluorodeoxyglucose (FDG). Here, we explored the cellular mechanism and signaling pathways that can explain the relation between EGFR and breast cancer cell glucose metabolism. FDG uptake, lactate production and hexokinase (HK) activity were measured, and proliferation assays and western blots were performed. EGF stimulated an increase of FDG uptake in EGFR-positive T47D and MDA-MB-468 cells, but not in MCF-7 cells. In T47D cells, the effect was dose-dependent and was accompanied by increased lactate production, indicating a shift toward glycolytic flux. This metabolic response occurred through enhanced HK activity and upregulated glucose transporter 1 (GLUT1) expression. EGFR stimulation also increased T47D cell proliferation. Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects. EGFR stimulation induced MAP kinase (MAPK) and PI3 kinase (PI3K) activation. Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002. Increased FDG uptake was also completely abrogated by PI3K inhibition but was uninfluenced by MAPK inhibition. These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling.
Seoul virus (SEOV) poses a worldwide public health threat. This virus, which is harbored by Rattus norvegicus and R. rattus rats, is the causative agent of hemorrhagic fever with renal syndrome ...(HFRS) in humans, which has been reported in Asia, Europe, the Americas, and Africa. Defining SEOV genome sequences plays a critical role in development of preventive and therapeutic strategies against the unique worldwide hantavirus. We applied multiplex PCR-based next-generation sequencing to obtain SEOV genome sequences from clinical and reservoir host specimens. Epidemiologic surveillance of R. norvegicus rats in South Korea during 2000-2016 demonstrated that the serologic prevalence of enzootic SEOV infections was not significant on the basis of sex, weight (age), and season. Viral loads of SEOV in rats showed wide dissemination in tissues and dynamic circulation among populations. Phylogenetic analyses showed the global diversity of SEOV and possible genomic configuration of genetic exchanges.
Peripheral regulatory T cells (pTregs) are a highly immunosuppressive fraction of CD4+ T cells. We aimed to evaluate the clinical significance of pTregs in patients with gastric cancer and to ...determine the correlation between pTregs and immune cell infiltration in tumor microenvironment. pTregs status was determined by assessing the pTreg/total T-cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation, so-called Cellular Ratio of Immune Tolerance "ImmunoCRIT") using methylation analyses in 433 patients with gastric cancer who received curative surgery. Among 422 evaluable patients, 230 (54.5%) had high ImmunoCRIT (> 21.0). Patients with high ImmunoCRIT had significantly shorter disease-free survival (DFS) and overall survival (OS) than those with high ImmunoCRIT (p = 0.030, p = 0.008, respectively). In multivariate analysis, high ImmunoCRIT kept a prognostic role for shorter OS (hazard ratio HR 1.9, 95% confidence interval CI 1.4-2.9; p = 0.005). CD3+ cell density and CD4+ cell density was significantly higher within the tumor in high ImmunoCRIT group than those in low ImmunoCRIT group (CD3+ cell, 202.12/mm.sup.2 vs. 172.2/mm.sup.2, p = 0.029; CD4+ cell, 56.5/mm.sup.2 vs. 43.5/mm.sup.2, p = 0.007). In conclusion, the peripheral ImmunoCRIT determined by epigenetic methylation analysis provides prognostic information in resected gastric tumors.
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