10588 Background: Genetic testing in gastroesophageal cancer has been limited to those with hereditary cancer syndromes, restricting understanding of the impact of germline variants in sporadic cancers. Our study expands this by exploring germline and somatic characteristics in a broad Chinese cohort, enhancing risk assessment and guiding treatment strategies in a wider population. Methods: From October 2017 to April 2023, we retrospectively analyzed 2596 Chinese gastroesophageal cancer (GEC) patients, including 2003 with gastric cancer (GC), 196 with gastroesophageal junction cancer (GEJC), and 397 with esophageal cancer (EC). A 520-gene panel including 62 genes associated with cancer predisposition, was employed for genomic profiling of paired tumor and white blood cell samples. The pathogenicity of germline variants was determined according to ACMG guidelines. Results: In this retrospective cohort, the proportion of patients carrying pathogenic/likely pathogenic (P/LP) germline variants was 5.3% in GC, 5.6% in GEJC, and 5.0% in EC, respectively. Notably, genes associated with HRR exhibited the highest rates of P/LP germline mutations in GEC (94, 3.7%), with the majority occurring in non-BRCA HRR genes (77, 3.0%). The top five genes with the highest mutation rates were ATM, PALB2, FANCA, CHEK2, and RAD54L. Compared to the East Asian population without cancer in the genomAD database, a higher proportion of P/LP germline mutations were found in the CDH1(Inf [6.46-Inf], p < 0.001), PALB2 (5.60 [1.61-13.09], p = 0.002), SDHA (8.99 [1.29-99.42], p = 0.012), ATM (2.15 [1.08-4.09], p = 0.02), and CHEK2 (3.83 [1.06-13.32], p = 0.02) genes in GC. Similarly, significant increases in PALB2 (10.36 [2.32-37.28], p = 0.002) and ATM (4.42 [0.86-14.33], p = 0.036) were also observed in EC and GEJC. The HRR P/LP variant group exhibited a higher incidence of biallelic inactivation (loss of wildtype allele) compared to the B/LB variant group (24.7% vs 6.6%, p<0.001). Moreover, the similar trend was observed for the moderately/uncertainly penetrant gene ATM and FANCA (38.5% vs 0.6%, p < 0.001; 42.9% vs 9.8%, p = 0.025), which suggests that ATM and FANCA may be associated with a high risk. The HRR genes ATM(56 vs 61, p = 0.052), CDH1(33 vs 61, p = 0.003), and FANCI(48 vs 61, p = 0.041) with P/LP variants were associated with a younger age of onset. Carriers of HRR P/LP variants had less prevalent somatic TP53 variants in GC and GEC and higher HRD score compared to non-carriers (p=0.005). Conclusions: Our research delineates the germline P/LP variant landscape in Chinese GEC, revealing the significant role of HRR P/LP variants. The presence of P/LP variants in HRR genes in GEC is linked to distinct disease characteristics and progression, underscoring their importance in guiding personalized treatment approaches and risk evaluation.

3544 Background: Signet-ring cell carcinoma (SRCC) of the rectum and sigmoid colon is a rare and highly malignant challenge in clinical practice. Although high PD-1+CD8+ tumor-infiltrating lymphocyte (TIL) infiltration has been reported as a positive prognostic factor in gastric cancer, pancreatic cancer, etc., its role in colorectal SRCC remains unclear. This study aims to explore the immune landscape of colorectal SRCC and its prognostic implications. Methods: The study included 34 patients with stage II-IV SRCC of the rectum and sigmoid colon. The immune contextures of tumor tissues were characterized using multiplex immunofluorescence assays and compared with a cohort of 57 cases of stage II-IV AC. The ratio density and spatial distribution of CD3 + , CD8 + , PD-1 + , PD-L1 + cells, M1/M2 macrophages, and NK cells were quantitively analyzed in both parenchymal (p) and interstitial (i) regions. Characteristics of immune cell infiltration and their prognostic value for long-term survival were investigated in SRCC cases. Results: Compared to AC, SRCC exhibited significantly higher infiltration of CD8+ and CD3+ iTILs in the interstitial region (P=0.00024; P=0.00321, respectively) and elevated CD8+ pTILs infiltration in tumor parenchyma (P=0.041). Conversely, parenchymal infiltration of TILs co-expressing PD-1 was significantly lower in SRCC than AC (PD-1+CD8+ pTILs: P=0.00035; PD-1+CD3+ pTILs: P=5.0e-05). SRCC showed significantly lower infiltration of M1 macrophages in both parenchyma and interstitium (P=0.0035; P=5.4e-09, respectively), lower interstitial infiltration of M2 macrophages (P=1.5e-05), and a borderline lower parenchymal infiltration of M2 macrophages (P=0.0522), compared to AC. Additionally, patients with high parenchymal or interstitial infiltration of PD-1+CD8+ TILs exhibited significantly longer DFS (P=0.00024; P=0.0041, respectively) and OS (P=0.011; P=0.0044, respectively) than those with low infiltration. Multivariate analysis indicated that the level of PD-1+CD8+ pTILs infiltration is an independent prognostic factor for DFS, being independent of CEA levels and TNM stage (P = 0.018; P = 0.02, respectively). Among patients with normal CEA level or of stage II-III, high level of PD-1+CD8+ pTILs infiltration was still associated with significantly improved DFS (P<0.0001; P=0.00018, respectively) and OS (P=0.00021; P<0.0001, respectively). Conclusions: SRCC of rectum and sigmoid colon exhibits distinct immune profiles compared to conventional AC, characterized by higher infiltration of CD8+ and CD3+ TILs, but lower infiltration of PD-1+CD8+ TILs. The unique immune landscape in SRCC, particularly the level of PD-1+CD8+ TILs infiltration and its positive predictive value for DFS and OS, provides new perspectives for immune-based stratification and therapeutic strategies for this clinically significant cancer subtype.

e13592 Background: Neoadjuvant immunochemotherapy has great potential to revolutionize the treatment of gastrointestinal cancer. However, effective biomarkers to classify responders from non-responders are still lacking. We aimed to build a response prediction model using multiplex immunofluorescence (mIF) images from patients with gastrointestinal cancer. Methods: We proposed a graph neural network-based (GNN) approach based on the pre-treatment mIF samples collected from 77 patients, including 30 gastric cancer (GC) patients, 34 colorectal cancer (CRC) patients, and 13 esophageal cancer (ESCA) patients. All the tissue samples were stained by two panels of mIF agents, namely Panel-A (CD3, CD8, PD1, PD-L1) and Panel-B (CD56, CD68, CD163). Cell coordinates, agent densities, and cell morphology features were used to generate cell graphs for model training. Results: Initially, we trained a pan-cancer GNN model for each panel and assessed its performance on the patch- and patient-level using five-fold cross-validation. The Panel-A model achieved higher areas under the receiver operating characteristic curve (AUROC) (patch-level: 0.71 ± 0.036, patient-level: 0.65 ± 0.010) than the Panel-B model (patch-level: 0.59 ±0.017, patient-level: 0.62 ± 0.021) and conventional mIF-based markers (i.e., positive cell ratios/counts of fluorescence agents, AUROC: 0.34 ~ 0.54). Specifically, the performance of CRC was better in the Panel-A model (patch-level: 0.75± 0.053, patient-level: 0.76 ± 0.053) than that in Panel-B (patch-level: 0.52 ± 0.027, patient-level: 0.60 ± 0.028), while the performance of GC was better in Panel-B (patch-level: 0.64 ± 0.030, patient-level: 0.71 ± 0.034) than that in Panel-A (patch-level: 0.53 ± 0.019, patient-level: 0.51 ± 0.018). The AUROCs of both panels of ESCA were less than 0.5, reflecting feature differences associated with treatment response between ESCA and GC/CRC. Furthermore, discrepancies of GC and CRC between Panel-A and -B motivated us to further optimize the performance for individual cancer types using transfer learning (TL). The GC TL-model performance (patch-level: 0.691±0.025, patient-level: 0.751 ± 0.046) was improved compared with the pan-cancer model, but not for the CRC TL-model (patch-level: 0.636 ± 0.066, patient-level: 0.697 ± 0.039). Moreover, the best patient-level specificity and sensitivity under the optimal Youden-Index were 70% and 88% for CRC, and 93% and 62% for GC. Conclusions: The GNN-based approach using mIF images demonstrated promising potential in predicting the immunochemotherapy response of gastrointestinal cancer patients, despite the limited number of samples were curated. The performance variation among cancer types indicated the cancer heterogeneity and the necessity of building single-cancer models when more data becomes available.

Without treatment, familial adenomatous polyposis (FAP) patients will inevitably develop colorectal cancer (CRC) during lifetime. Yet, surgical trauma is a high risk of desmoid tumor (DT), one of the main causes of death in FAP patients. So far, the timing for colectomy is primarily based on the clinician's experience and the patient's preference; most patients undergo surgery at mid-20's. In this study, we analyzed the germline mutation distribution in 35 FAP patients from different families, 16 of them diagnosed with DTs. We also investigated the association between the molecular alterations and the clinicopathological features. Capture-based targeted sequencing using a panel of 520 genes was performed on tumor tissue and paired normal mucosa or white blood cells from 18 FAP probands who were initially diagnosed with CRC. Of all 35 FAP patients, 30 (85.7%) of them harbored germline APC mutations scattered from codon 161 to 1578. The mutations in the 16 DT patients scattered from codon 457 to 1578. All three patients with the mutation at the 3' of 1444 codon were diagnosed with DT. The percentage of high-risk DT (stage III or IV) harboring mutations at the 5' of 1062 or 1062-1578 was 14.3% and 77.8%, respectively, and all three patients with 3' of 1399 codon mutation had high risk. In addition, by using public database, we compared 140 FAP patients with DT to all 1880 FAP patients on the Leiden Open Variation Database and found that the odd ratio of DT in codon 159 to 495 was 0.34, while in codon 1310 to 2011 was 2.36. Compared to sporadic CRCs, the somatic spectrum of FAP CRCs was similar to the early onset CRCs, with higher TP53 (94.1%) and lower somatic APC mutations (65.7%), but the KRAS mutation rate was the highest (58.5%). One of the 18 FAP CRCs was identified as microsatellite instability-high (MSI-H), with tumor mutation burden (TMB) of 115.65 mut/Mb. Given that no TP53 mutations were detected in the low- and high-grade adenomas, ctDNA TP53 sequencing might be used for the close monitoring before FAP colectomy. In conclusion, except mutations at the 5' end of APC (5' to 495), all FAP patients need to consider the risk of DT after colectomy. The chance of life-threating DTs was higher in patients with 3' 1062 codon mutation and peaked in patients with 3' 1399 codon mutation. Scheduled monitoring of TP53 ctDNA is proposed to be a novel tool for optimizing the operation time.

BACKGROUND Solitary fibrous tumor (SFT) of the central nervous system is rare. It is predominantly benign and rarely malignant. There is no established standardized treatment regimen for malignant intracranial SFTs. CASE SUMMARY We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes. She underwent craniotomy, and the mass was resected. Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80% of tumor cells. Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53. At 1.5 mo after surgery, head magnetic resonance imaging revealed that the tumor had recurred. The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy. The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle. Following this regimen, the patient achieved stable disease for > 17 mo. Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed. CONCLUSION This is the first reported case of SFT of the central nervous system treated with surgery, radiotherapy and anlotinib. This regimen may be an effective treatment option for malignant intracranial SFT patients.

The rapid identification of bacterial antibiotic susceptibility is pivotal to the rational administration of antibacterial drugs. In this study, cefotaxime (CTX)-derived resistance in Salmonella typhimurium (abbr. CTX(R)-S. typhimurium) during 3 months of exposure was rapidly recorded using a portable Raman spectrometer. The molecular changes that occurred in the drug-resistant strains were sensitively monitored in whole cells by label-free surface-enhanced Raman scattering (SERS). Various degrees of resistant strains could be accurately discriminated by applying multivariate statistical analyses to bacterial SERS profiles. Minimum inhibitory concentration (MIC) values showed a positive linear correlation with the relative Raman intensities of I-990/I-1348, and the R-2 reached 0.9962. The SERS results were consistent with the data obtained by MIC assays, mutant prevention concentration (MPC) determinations, and Kirby-Bauer antibiotic susceptibility tests (K-B tests). This preliminary proof-of-concept study indicates the high potential of the SERS method to supplement the time-consuming conventional method and help alleviate the challenges of antibiotic resistance in clinical therapy.

Introduction:NF-κB signaling is involved in a wide range of biological processes including cell proliferation, cell survival and immunity. Meanwhile, as one of the major oncogenic pathways, its upregulation has been observed in many cancer types. Compared with canonical NF-κB signaling, its non-canonical branch was much less studied in cancerous context.Methods:In this study, we leveraged multi-omics data across multiple platforms to investigate the activity of non-canonical NF-κB signaling in low-grade glioma (LGG) and explore its connection with molecular characteristics of LGG.Results:We found that non-canonical NF-κB signaling could classify LGG patients into subgroups with significant survival difference. Non-canonical NF-κB-low group enriched with oligodendroglioma featured by CIC mutations and 1p19q co-deletion. On the another hand, LGG in non-canonical NF-κB-high group showed high frequency of EGFR mutations but relatively low frequency of IDH mutations. In addition, LGG in this group reflected immunosuppressive environment characterized by high level of cytotoxic T cell exhaustion and macrophage M2 infiltration. More comprehensive evaluation implied that LGG in non-canonical NF-κB-high group reflected significantly higher immunogenicity. Through a series of feature selection technique, we developed a model that can predict the prognosis of LGG patients in a cost-effective way.Conclusion:Our analysis demonstrated the prognostic value of non-canonical NF-κB signaling in LGG. The survival difference between non-canonical NF-κB stratified groups may be explained by their distinct molecular characteristics as well as cellular context. Our prognostic model may help in offering better therapeutic strategy and clinical management.

Wingless/Int-1 (Wnt) signaling is one of the most well-known oncogenic pathways. Numerous studies have uncovered an aberrant expression of Wnt in cancer and its association with multiple oncogenic processes, such as cell proliferation, epithelial–mesenchymal transition (EMT), and invasiveness. Most previous studies mainly focused on the canonical branch of Wnt signaling pathway, i.e., Wnt/β-catenin signaling. The Wnt/planar cell polarity (PCP) signaling pathway, as the most recently described branch of Wnt signaling, was much less investigated in oncology research. In this study, we thoroughly characterized the activity of the Wnt/PCP regulation pathway in low-grade glioma (LGG) patients. Subtyping based on the expression pattern of the Wnt/PCP regulation pathway revealed three (C1–C3) subgroups with significant survival differences. Each group displayed distinct genomic characteristics. For instance, C1 was enriched with capicua transcriptional repressor (CIC) truncating mutations and 1p19q codel. C2 was characterized with tumor protein p53 (TP53) and ATRX chromatin remodeler (ATRX) inactivating mutations but depletion of telomerase reverse transcriptase (TERT) promoter mutations. C3 showed elevated malignancy reflected from several oncogenic characteristics, such as tumor heterogeneity and cell stemness, and demonstrated the worst survival outcome. In addition, C3 showed elevated macrophage segregation via induction of cytokines that are able to enhance the permeability of the brain–blood barrier (BBB). Lastly, we developed a prognostic model based on the risk score system. Validation indicated that our model can independently predict the prognosis of LGG patients.

Abstract Introduction: RNA-editing is widespread across human genome. Previous studies have observed that RNA editing level differs significantly across multiple cancer types and may influence cancer development. Increased level of RNA editing has been found to correlate with enhanced tumorigenesis in some cancers but reduced tumorigenesis in others. In brain tumor, the RNA editing landscape has not been well characterized partially due to the difficulty of sample accessibility. We performed multi-regional RNA-Seq on cancerous, peritumoral and distant tissue collected from 40 brain cancer patients. Our aim is to depict the landscape of RNA editing and to comprehend the relevance of RNA editing with other molecular characteristics of brain cancer. Methods: We collected 40 cancerous brain tissue sample (30 LGG and 10 GBM), each coupled with a peritumoral tissue and a distant tissue. These 120 samples were subjected to RNA-Seq sequencing. RNACocktail was applied for identification of RNA editing events. RADAR and ANNOVAR were used for identification and annotation of A-to-I editing sites. RNAEditingIndexer was used to estimate sample-wise editing level denoted as AEI. Pathway enrichment analysis was performed using GSEA. Statistical difference of molecular characteristics between sample groups was calculated using either Wilcoxon signed rank test or Kruskal-Wallis test. Results: A total number of 21,105 and 5,634 informative editing events were identified in LGG and GBM respectively. As expected, most editing events were located within Alu element of intronic and 3'UTR region. In both LGG and GBM, RNA editing level showed decreasing trend from distant to peritumoral to cancerous samples. Compared with normal tissue, we found 5.12‰ up-regulated events and 16.92‰ down-regulated events in LGG samples. Similar pattern was found in GBM as well. We found two editing sites with significant editing differences (adjust p-value < 0.05) within coding region of GRIK2 and NEIL1 gene. In addition, numerous editing sites showed statistical correlation other molecular/pathological characteristics such as IDH1 mutation, existence of seizure, MGMT methylation and pathological classification. At sample level, the same decreasing trend of RNA editing level was consistently observed from distant to cancerous tissue. Enrichment analysis showed that editing level was positively correlated with neural transmission and oncogenic related pathways. In addition, sample level editing was significant different between WHO as well as pathological classification. Citation Format: Cheng Yan, Jun Wu, Dan Wang, Lan Su, Yufei Yang. Multi-regional RNA-Seq reveals pattern of RNA-editing in brain tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2168.

Abstract Background: In 2010, scientific community reached a consensus regarding its subtyping (WNT/β-catenin, Sonic Hedgehog, Group 3, and Group 4). Research demonstrated that different subtype displays distinct genotypic characteristics as well as prognostics. Currently, transcriptomic profiling via NanoString is well-accepted for medulloblastoma subtyping. However, this platform requires high quality RNA sample. An alternative approach is in need for more robust and accurate subtyping. In this study, we explored the feasibility of using machine learning approach for medulloblastoma subtyping based on genome-wide SCNVs. Method: We retrieved SNP array CEL data of 1097 medulloblastoma (GSE37385) from GEO. 800 samples were remained for further analysis after QC. 32 medulloblastoma samples were collected from Robinson G, et's study as independent validation set. Penncnv was used to calculate log R ratio and B allele frequency. DNAcopy was used for CNV segmentation. GISTIC2 was applied to obtain arm and focal SCNAs. A number of classifiers were trained using SCNAs as well as age and gender. Feature selection was conducted in a model specific manner. Model performance was assessed using AUROC. Result: Benchmark on validation set showed that accuracy of Naïve Bayes, Random Forest, AdaBoost, Logistic Regression and SVM are 76.25%, 75%, 75%, 77.5% and 80.62% respectively. AUROC is 90.98%, 92.3%, 91.32%, 92.1% and 92.02% in corresponding order. The relatively overfitting and comparable performance across most models implied that SCNAs own moderate predictive power in medulloblastoma subtyping. Generally, SVM with linear kernel demonstrated superior and balanced performance than other models. Feature importance evaluation via Random Forest and AdaBoost showed better predictive power of arm-level SCNAa of 6p, 6q, 7p, 7q, 16q, 17p, 17q, consistently with previous studies. Focal SCNAs on SIRPB1 and age owned high predictive power. Nanostring performs poorly on distinguishing Group 3 and Group 4. Our method showed same tendency, indicating transcriptomic as well as genomic similarity between these two groups. We decided to permit 10% of validation samples as ‘prediction failure' for those with highly similar SCNAs characteristics. Upon this modification, accuracy of most model raised 3% on average. Conclusion: Our study evaluated the feasibility of using genome-wide SCNAs profile for medulloblastoma subtyping. Benchmark showed moderate predictive power using SCNAs. Among a number of machine learning approaches, SVM with linear kernel demonstrated superior performance. Citation Format: Cheng Yan, Dan Wang, Lan Su, Yufei Yang, Hao Du. A machine learning approach for accurate medulloblastoma subtyping using arm-level SCNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 155.

PURPOSEGliomas are life-threatening brain tumors, and the extent of surgical resection is one of the strongest influences on survival rate. However, the proper distinction of infiltrated tissue remains elusive. The aim of this study was to use multimodal analyses to demarcate peritumoral tissue (PT) from tumoral (TT) and healthy tissue (HT).METHODSA total of 40 patients with histologically confirmed glioma were recruited. We analyzed resting-state functional magnetic resonance imaging (rs-fMRI) using the voxel-based mean blood-oxygen-level-dependent (BOLD) signal and the corresponding structural MRI (s-MRI) alongside RNA sequencing, whole-exome sequencing, and histology results of biopsy samples obtained from PT, HT, and TT.RESULTSWe demarcated a functionally defined PT area where the mean BOLD signal gradually decreased near the edge of the tumor and extended beyond the TT borders (as defined by s-MRI), which was confirmed on a case-by-case basis. Correspondingly, genetic analyses showed a gene expression pattern and mutational landscape of the PT that were distinct from that seen in HT and TT. The genetic characterization of PT relative to HT and TT converged with the MRI-defined PT zones. This was confirmed in three individual cases after additional histologic analysis. A wider PT was associated with a longer progression-free survival, which suggests PT might act as an intermediate area between TT and HT.CONCLUSIONCombined multimodal imaging and genetic analyses can allow for an objective demarcation of the PT in glioma and a robust classification of the degree of infiltration of the PT. These findings could help improve both neurosurgical resection and radio-oncologic therapy.

Abstract Introduction: Aberrant activity of NF-kB has been observed across several cancer types. The current understanding is that the constitutive activation of NF-kB enhances the expression of genes that promote cell proliferation as well as prevent cells from apoptosis. Previous studies have shown that, compared with other cancer types, glioma appears with much significant over-expression of NF-kB. This implies that glioma may be a better subject to elucidate the activity of NF-kB during tumorigenesis. Here we present an analysis aiming to characterize the oncogenic involvement of NF-kB in glioma. Method: We retrieved RNA-Seq expression data of glioblastoma (GBM), low-grade glioma (LGG) as well as other seven major cancer types from TCGA repository. In addition, we collected a total number of 120 tumor samples comprising of 80 GBM and 40 LGG. RNA-Seq experiment was carried out according to standard protocol. Data quality was assessed at multiple steps. In correlation analysis, a number of oncogenic and immune genes / pathways were empirically pre-defined. Pearson coefficient was measured. Expression enrichment analysis was performed using either GSEA or ssGSEA. Immune cell infiltration was assessed using ESTIMATE. Results and conclusion: Pan-cancer analysis shown that, compared with peripheral non-tumor tissue, all five NF-kB member genes, NFKB1, NFKB2, REL, RELA and RELB, are significantly up-regulated in tumor tissue of GBM and LGG, but not in other cancer types. Except previously reported association with EGFR mutation, we also observed that TP53 mutation significantly correlates with over-expression of NF-kB in LGG. CDKN2A and CDKN2B deletion moderately correlate with over-expression of NFKB1,RELB and REL. In addition, RAS and ERBB signaling pathway positively correlates with NF-kB pathway in both GBM and LGG. This is consistent with established cross-talk between these genes. WNT signaling pathway positively correlates with NF-kB in GBM while negatively correlates with NF-kB in LGG. NF-kB regulates WNT signaling through LZTS2 under specific physiological conditions. Our results shown that LZTS2 is up-regulated in LGG while down-regulated in GBM suggesting that NF-kB regulates WNT through LZTS2 in a bidirectional manner. In regulating immune environment, NF-kB expression positively correlates with major immune infiltrates as well as cytokines responsible for modulating the penetrance of blood-brain barrier (BBB), indicating that NF-kB recruit immune cells in response to stimuli in brain despite the existence of BBB. In sum, NF-kB seems to impose rather similar impact on glioma as on other non-CNS solid tumor, i.e. recruitment of immune infiltrates. On the other hand, NF-kB behaves differently in regulating WNT signaling pathway in GBM and LGG. How differential activation of WNT signaling eventually contributes to phenotypical difference between GBM and LGG is to be investigated in further studies Citation Format: Cheng Yan, Lan Su, Xin Qi, Yufei Yang, Jun Wu. Oncogenic involvement of NF-kB signaling pathway in glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4735.

Rapid detection of food-borne pathogens is the most critical and urgent issue among all the current food safety problems. As enhanced substrate, nanoparticles are widely used in surface enhanced Raman scattering (SERS) because of unique optical and physicochemical properties. In this study, Au nanoparticles with monodisperse and good reproducibility were synthesized by using sodium citrate reduction method. Applying Au nanoparticles sol as enhanced substrate, a portable Raman spectrometer had been applied for rapid detection of single and mixture pathogenic bacterial contamination by SERS. The results indicated that Escherichia coli, Salmonella typhimirium, Shigella flexner and Staphylococcus aureus showed specific Raman phenotypes at 600∼1700 cm-1. Generally, different bacteria could be easily and instantly recognized by its Raman phenotypes. The PC-LDA classification model was set up by combined bacterial Raman phenotypes with the multivariate statistical analysis. With the short-time inoculation, four enteropathogenic bacteria could be rapidly, precisely, sensitively and specifically identified. Furthermore, the model also had a good ability to predict the mixed contamination. This research provides the possibility of rapid detection in the food and biomedical fields.

In this paper, the surface-enhanced Raman scattering (SERS) is used as an analytical tool for the detection and identification of pathogenic bacteria of Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium). Compared with normal Raman signal, the intensity of SERS signal is greatly enhanced. After processing all SERS data, the obvious differences between the SERS spectra of two species are determined. And applying the chemometric tools of principal component analysis and hierarchical cluster analysis (PCA-HCA), the SERS spectra of two species are distinguished more accurately. The results indicate that SERS analysis can provide a rapid and sensitive method for the detection of pathogenic bacteria.

Chromium contaminated drug capsules drew much of world's attentions. Although trace amount of chromium allowed to existence in the drug capsules, but the combined effects of chromium with other drug chemicals remain unclear. Therefore, the combined genotoxicity of hexavalent chromium [Cr (VI)] with nitroso drug chloroethylnitrosourea (ACNU) was examined using the Salmonella mutagenicity assay. The results showed that Cr (VI) and ACNU produced a dose-dependent increase in the revertants in TA 98 and TA 100 strains. In the individual chemical mutation assay, the positive mutagenicity response for Cr (VI) doses was above 2 ilk per plate, and for ACNU above 5 mg per plate. In binary chemical mutation assay, the straightforward positive results could even be detected when the dose of Cr (VI) and ACNU both,down to 1 mg per plate. It was indicated that neither Cr (VI) nor ACNU individually caused more genotoxicity to bacterial DNA at low levels. However, the two, working together, had significant revertant mutation effects. This means the combined genotoxicity effects of Cr (VI) and ACNU are more harmful than the individual exposure.

乙型肝炎作为一种发病率高、死亡率高的传染性疾病,已严重威胁人类健康,乙肝病毒(hepatitis B virus,HBV)是诱发乙型肝炎的重要病因.目前,最主要的治疗方法是运用抗病毒药物控制病情,但这些药物都不能完全治愈乙型肝炎且复发率高.近年来,RNA干扰技术(RNA interference,RNAi)逐渐成为有效、快速治疗乙型肝炎的新疗法.利用RNA干扰技术体外合成针对HBV基因的siRNA,选择适当的载体将其运送至靶细胞,使HBV基因沉默,从而抑制病毒复制,可有效达到治疗乙肝的效果.本文围绕siRNA沉默HBV基因的设计原理、递送载体、靶向策略、以及治疗效果与应用前景等方面进行了系统综述,为今后siRNA治疗乙肝的临床应用提供参考.