Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

Background Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). Conclusions Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC

Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

ECC: Extrahepatic cholangiocarcinoma; ICC: Intrahepatic cholangiocarcinoma; IG: Intraductal growth; LINE-1: Long interspersed element-1; MF: Mass-forming; PI: Periductal infiltrative; TNM: Tumor, node, and metastasisAbstract Background DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5′ untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. Methods A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. Results Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. Conclusions Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.This work was supported by a grant from the National Research Foundation (NRF) grants funded by the Korean Ministry of Science, ICT and Future Planning (2011–0030049 and 2016M3A9B6026921), a grant from the Priority Research Centers Program through the NRF (2009–0093820), and a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute funded by the Korean Ministry of Health and Welfare (HI14C1277). The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of the data, or in the writing of the manuscript

Effects of Seed Endophytic Bacteria on Life History and Reproductive Traits in a Cosmopolitan Weed, <i>Capsella bursa-pastoris</i>

Diverse bacteria inhabit plant seeds, and at least some of them can enhance plant performance at the early developmental stage. However, it is still inconclusive whether seed bacteria can influence post-germination traits and their contribution to plant fitness. To explore the evolutionary and ecological consequences of seed endophytic bacteria, we isolated four bacterial strains from the seeds of an annual weedy plant species, Capsella bursa-pastoris, and conducted a common garden experiment using seeds inoculated by isolated bacteria. Seeds infected by bacteria tended to germinate in spring rather than in autumn. Bacterial treatment also altered the expression of plant life history and reproductive traits, including flowering dates, rosette diameter at bolting, number of inflorescences, and fruit production. The results of the path analyses suggested that such effects of bacterial treatments were due to bacterial inoculation as well as germination delayed until spring. Spring germinants with bacterial infection showed a weaker association between post-germination traits and relative fitness than those without bacterial infection. These results suggest that seed bacteria likely affect the expression of post-germination traits directly or indirectly by delaying the germination season. An altered contribution of plant traits to relative fitness implies the influence of seed bacteria on the strength of natural selection

Additional file 2: Figure S2. of Improved results of LINE-1 methylation analysis in formalin-fixed, paraffin-embedded tissues with the application of a heating step during the DNA extraction process

(A) Application of a heating step during DNA extraction increased the mean number of methylated CIMP panel markers from 0.8 to 0.9. Cases with no methylation of CIMP panel markers decreased from 66.9 to 61.2%. (B) Application of a heating step allowed identification of 1.8% more CIMP-high colorectal cancer cases. (PDF 238 kb

Additional file 1: Figure S1. of Improved results of LINE-1 methylation analysis in formalin-fixed, paraffin-embedded tissues with the application of a heating step during the DNA extraction process

Methylation levels of the four LINE-1 CpG sites for four xenograft DNA samples (MKN-45, SNU-638, SW620, and LoVo xenograft tumors) with heating at 95 °C for 30 or 60 min. Both the paired Student’s t test and the paired Wilcoxon signed-rank test were performed to compare the mean methylation values of the four CpG sites between paired fresh-frozen and formalin-fixed, paraffin-embedded tissue samples. P values in the bar graph represent the values of both the parametric and the non-parametric tests. (PDF 244 kb

Additional file 1: of Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

A. Scatter plot of LINE-1 methylation and percentage of non-neoplastic stroma cells in dissected tumor areas. B. Box plot of LINE-1 methylation by grouping ICCs into 3 subsets according to percentage of non-neoplastic stroma cells. Analysis of the relationship between LINE-1 methylation level and stroma ratio of tumor area did not show significant correlation between them. No significant difference was seen in tumoral LINE-1 methylation level between four subsets of ICCs according to percentage of non-neoplastic cells (<10%, 10–19%, 20–30%, >30%). (JPEG 307 kb

Enhancement of Photoresponse on Narrow-Bandgap Mott Insulator alpha-RuCl3 via Intercalation

Charge doping to Mott insulators is critical to realize hightemperature superconductivity, quantum spin liquid state, and Majorana fermion, which would contribute to quantum computation. Mott insulators also have a great potential for optoelectronic applications; however, they showed insufficient photoresponse in previous reports. To enhance the photoresponse of Mott insulators, charge doping is a promising strategy since it leads to effective modification of electronic structure near the Fermi level. Intercalation, which is the ion insertion into the van der Waals gap of layered materials, is an effective charge-doping method without defect generation. Herein, we showed significant enhancement of optoelectronic properties of a layered Mott insulator, alpha-RuCl3, through electron doping by organic cation intercalation. The electron-doping results in substantial electronic structure change, leading to the bandgap shrinkage from 1.2 eV to 0.7 eV. Due to localized excessive electrons in RuCl3, distinct density of states is generated in the valence band, leading to the optical absorption change rather than metallic transition even in substantial doping concentration. The stable near-infrared photodetector using electronic modulated RuCl3 showed 50 times higher photoresponsivity and 3 times faster response time compared to those of pristine RuCl3, which contributes to overcoming the disadvantage of a Mott insulator as a promising optoelectronic device and expanding the material libraries