Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric ...cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene.
We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models.
SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining (P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling.
Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.
Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their ...sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
Telomerase has attracted much attention as a universal cancer biomarker because telomerase is overexpressed in more than 85% of human cancer cells while suppressed in normal somatic cells. Since a ...strong association exists between telomerase activity and human cancers, the development of effective telomerase activity assay is critically important. Here, a nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is reported for detection of telomerase activity in various cancer cells and tissues. The nanogap‐rich Au NWs are constructed by deposition of nanoparticles on single‐crystalline Au NWs and provided highly reproducible SERS spectra. The telomeric substrate (TS) primer‐attached nanogap‐rich Au NWs can detect telomerase activity through SERS measurement after the elongation of TS primers, folding into G‐quadruplex structures, and intercalation of methylene blue. This sensor enables us to detect telomerase activity from various cancer cell lines with a detection limit of 0.2 cancer cells mL−1. Importantly, the nanogap‐rich Au NW sensor can diagnose gastric and breast cancer tissues accurately. The nanogap‐rich Au NW sensors show strong SERS signals only in the presence of tumor tissues excised from 16 tumor‐bearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. It is anticipated that nanogap‐rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing.
A nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is developed for ultrasensitive and specific detection of telomerase activity. The optimized nanogap‐rich Au NW can provide highly reproducible and strong SERS signals. Using nanogap‐rich Au NW SERS sensors, telomerase activities of cancer cells and tumor tissues are successfully detected, suggesting the potential applicability of nanogap‐rich Au NW SERS sensor in cancer diagnosis.
Background & aims
Contrast‐enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI‐RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma ...(HCC). We performed a meta‐analysis to determine the diagnostic performance of the CEUS LR‐5 for HCC and the pooled proportions of HCCs in each CEUS LI‐RADS category.
Methods
We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI‐RADS. Random‐effects model was used to determine summary estimates of the diagnostic performance of CEUS LR‐5 and the pooled proportions of HCCs in each CEUS LI‐RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies‐2 tool.
Results
Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per‐observation sensitivity and specificity of the CEUS LR‐5 for diagnosing HCC were 69% (95% confidence interval CI, 64%–73%) and 92% (95% CI, 83%–96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0‐0%) for LR‐1, 1% (95% CI, 0%–4%) for CEUS LR‐2, 26% (95% CI, 14%–39%) for CEUS LR‐3, 77% (95% CI, 68%–86%) for CEUS LR‐4, 97% (95% CI, 95%–98%) for CEUS LR‐5, 57% (95% CI, 44%–69%) for CEUS LR‐M and 100% (95% CI, 93%–100%) for CEUS LR‐5V or TIV.
Conclusions
The CEUS LR‐5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI‐RADS categories.
Infiltrate and destroy: In an environment rich in protonating or oxidative species, such as the intracellular milieu of cancer cells, the main absorption band of spherical, water‐soluble polyaniline ...nanoparticles was red‐shifted to a near‐infrared (NIR) wavelength as a result of the formation of the emeraldine salt (see picture). The doped nanoparticles caused photothermal ablation of cancer cells upon NIR laser irradiation in vitro and in vivo.
Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and ...leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.
We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific.
Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
This study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative ...contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P < 0.001 internal validation; 0.652, P = 0.010 external validation) and the merged model (0.719, P < 0.001; 0.651, P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.
PDF
