Abstract Introduction: The detectability and prognostic significance of circulating tumor DNA (ctDNA) in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy (NAC) is unclear. The objective of this study was to investigate the rate of detection and prognostic value of KRAS mutant ctDNA in PDAC patients after treatment with NAC as assessed by digital droplet polymerase chain reaction (ddPCR). Methods: Patients with newly diagnosed, localized, PDAC were enrolled in a prospective cohort study. Peripheral blood samples were collected at diagnosis, after NAC, and after resection. DNA was extracted from patient plasma samples using the QIAamp Circulating Nucleic Acid Kit #55114 (Qiagen N.V., Venlo Netherlands). Each sample was probed (catalog number 10049550) for KRAS codon 12 exon 2 glycine substitutions for aspartic acid (G12D), valine (G12V), and arginine (G12R). Kaplan-Meier, log-rank, and Cox regression survival analyses were performed. Results: 84 patients were included in the analysis. Patients were most commonly male (53.6%) and had tumors that were radiographically resectable (57.1%). After diagnosis, 79.8% of patients received NAC and 57.1% of patients received curative-intent surgical resection. Samples were collected for analysis from 59 (70.2%), 56 (83.6%), and 45 (93.8%) patients at diagnosis, after NAC, and after resection, respectively. Mutant KRAS ctDNA was detected in 49.3% of patients at diagnosis, 69.6% of patients after NAC, and 54.1% of patients after resection, respectively. The median OS of the cohort was 25.1 months (12.0-not reached [NR]). Detection (hazard ratio [HR] 36.8, 95% confidence interval [CI] 2.9-461.4), copy number (HR 4.0 95% CI 1.6-10.2), and percentage mutation (HR 2.9 95% CI 1.2-6.8) of KRAS G12V ctDNA after resection were all independently associated with shorter OS. Mutant KRAS ctDNA detection was not associated with and OS at other study timepoints. There were 15 (17.9%) patients that cleared mutational ctDNA over the course of treatment. Clearance of ctDNA during NAC was associated with improved overall survival (OS) (18.4 mo. vs NR). Conclusions: In patients with PDAC treated with NAC, KRAS mutations are detectable in ctDNA by ddPCR in the majority of patients over the course of treatment. Detection, copy number, and percentage mutation of KRAS G12V after NAC and resection were each independently associated with shorter OS. Clearance of ctDNA is associated with improved OS. The results demonstrate that KRAS mutant ctDNA predicts prognosis after NAC and resection. Citation Format: Dominic Vitello, Dhavan Shah, Amy Wells, Larissa Masnyk, Madison Cox, Lauren Janczewski, John Abad, Kevin Dawravoo, Arlene D'Souza, Grace Suh, Robert Bayer, Massimo Cristofanilli, David Bentrem, Yingzhe Liu, Hui Zhang, Lucas Santana-Santos, Lawrence Jennings, Qiang Zhang, Akhil Chawla. Mutant KRAS in Circulating Tumor DNA Assessed by Digit Droplet PCR as a Biomarker in Pancreatic Cancer in Patients Treated with Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A009.
Abstract Chronic alcohol intoxication impairs multiple cognitive functions. According to the dual system model (DSM), the development of alcohol dependence (AD) involves the imbalance between the automatic-affective system and the reflective system. However, the cognitive functions of non-AD hazardous drinkers (HDs) remain unclear. The present study aimed to explore how the HDs process facial expressions differently from the healthy subjects. Sixteen HDs and seventeen control subjects (CSs) completed an emotional working memory (WM) task while the electroencephalogram (EEG) was recorded. We found that there was no significant group difference in behavioral performance between the two groups. In the ERP data, relative to the CSs, the HDs showed delayed latencies of P1 and N170. Moreover, the CSs showed significant differences between the amplitudes of neural/fear and disgust expressions while these differences were insignificant in the HDs. The current results suggest that the main deficits in the processing of facial expression in HDs existed in the early automatic-affective system instead of in the reflective system.
Abstract Background: Accurate measurement of intraocular pressure (IOP) after corneal refractive surgery is of great significance to clinic, and comparisons among various IOP measuring instruments are not rare, but there is a lack of unified analysis. Although Goldmann Applanation Tonometer (GAT) is currently the internationally recognized gold standard for IOP measurement, its results are severely affected by central corneal thickness (CCT). Ocular Response Analyzer (ORA) takes certain biomechanical properties of cornea into account and is supposed to be less dependent of CCT. In this study, we conducted the meta-analysis to systematically assess the differences and similarities of IOP values measured by ORA and GAT in patients after corneal refractive surgery from the perspective of evidence-based medicine. Methods: The authors searched electronic databases (MEDLINE, EMBASE, Web of science, Cochrane library and Chinese electronic databases of CNKI and Wanfang) from Jan. 2005 to Jan. 2019, studies describing IOP comparisons measured by GAT and ORA after corneal refractive surgery were included. Quality assessment, subgroup analysis, meta-regression analysis and publication bias analysis were applied in succession. Results: Among the 273 literatures initially retrieved, 8 literatures (13 groups of data) with a total of 724 eyes were included in the meta-analysis, and all of which were English literatures. In the pooled analysis, the weighted mean difference (WMD) between IOPcc and IOPGAT was 2.67 mmHg (95% CI: 2.20~3.14 mmHg, p < 0.0001), the WMD between IOPg and IOPGAT was -0.27 mmHg (95% CI: -0.70~0.16 mmHg, p = 0.2174). In the subgroup analysis of postoperative IOPcc and IOPGAT, the heterogeneity among the data on surgical procedure was zero, while the heterogeneity of other subgroups was still more than 50%. The comparison of the mean difference of pre- and post-operative IOP (∆IOP) was: mean-∆IOPg > mean-∆IOPGAT > mean-∆IOPcc. Conclusions: IOPcc, which is less dependent on CCT, may be more close to the true IOP after corneal refractive surgery compared with IOPg and IOPGAT, and the recovery of IOPcc after corneal surface refractive surgery may be more stable than that after lamellar refractive surgery.
The characteristics and application properties of feather keratin were reviewed and the mechanisms of keratin degradation were briefly discussed. The mechanisms of physical pressure, membrane potential and complex enzymes were introduced and three actions or processes of mechanical keratinolysis, sulphitolysis and proteolysis were discussed. The actions of sulphitolysis and proteolysis functioned in all the degradation process. Keratinase with keratin degrading capability was introduced and the utilization potential of keratin and keratinase were also discussed.
e18142 Background: Responsiveness of non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors has been confirmed to relate to mutations in the epidermal growth factor receptor (EGFR) signaling pathway genes. This study’s aim is to detect mutations in two important components of the EGFR signaling pathway, EGFR and KRAS, using a novel liquidchip technology, and to evaluate the correspondence between tumor and plasma DNA in the same patient. Methods: 58 advanced primary NSCLC ( IIIB or ‡W) tumor tissues and matched peripheral blood samples (MPBS) were obtained. The procedures for multiplex PCR, allele specific primer extension (ASPE) and hybridization were performed after DNA extraction. A novel liquidchip platform for simultaneous detection multiple alleles of DNA somatic mutations was applied to detect the EGFR and KRAS status in matched samples. Results: EGFR exon 19 and exon 21 mutation rate was detected to be 29.3% (17/58) and 17.2% (10/58) respectively in tumor tissues, while 20.7% (12/58) and 12.1% (7/58) in MPBS. Among those 27 patients who harbor either EGFR exon 19 or exon 21 mutations in tissues, 19 (70.4%) of them were detected to have the same mutations in their peripheral blood samples. EGFR exon 20 T790M mutations were found in one of the paired samples. All the patients who were detected to have wild-type EGFR in tissues were detected to have wild-type in MPBS as well. In 50 of 58 (86.2%) of the paired samples, the EGFR mutation status in the tumors was consistent with those in the MPBS. The KRAS exon 2 mutation was also found in both blood and tumor samples in one patient; however only in the blood of another patient, not in his tumor. Conclusions: The liquidchip technology may serve as an effective method for detecting multiple gene mutations. EGFR and KRAS gene mutations in blood DNA were highly consistent with the corresponding tissue samples, and therefore, peripheral blood could be used as an alternative sample to predict patients’ response to the anti-EGFR targeted therapy. Further studies to evaluate the clinical application are suggested.
Epstein-Barr virus (EBV) was the first virus identified to encode microRNAs (miRNAs). Both of viral and human cellular miRNAs are important in EBV infection. However, the dynamic expression profile of miRNAs during primary EBV infection was unknown. This study aimed to investigate the dynamic expression profile of viral and cellular miRNAs in infectious mononucleosis (IM) caused by primary EBV infection.The levels of viral and cellular miRNAs were measured in fifteen pediatric IM patients at three different time-points. Fifteen healthy children who were seropositive for EBV were enrolled in the control group. Relative expression levels of miRNAs were detected by quantitative real-time PCR (qPCR) assay.EBV-miR-BHRF1-1, 1-2-3P, miR-BART13-1, 19-3p, 11-3P, 12-1, and 16-1 in IM patients of early phase were significantly higher than in healthy children. Most cellular miRNAs of B cells, such as hsa-miR-155-5p, -34a-5p, -18b-5p, -181a-5p, and -142-5p were up-regulated; while most of cellular miRNAs of CD8 + T cells, such as hsa-miR-223, -29c-3p, -181a, -200a-3p, miR-155-5p, -146a, and -142-5p were down-regulated in IM patients. With disease progression, nearly all of EBV-miRNAs decreased, especially miR-BHRF1, but at a slower rate than EBV DNA loads. Most of the cellular miRNAs of B cells, including hsa-miR-134-5p, -18b-5p, -34a-5p, and -196a-5p increased with time. However, most of the cellular miRNAs of CD8 + T cells, including hsa-let-7a-5p, -142-3p, -142-5p, and -155-5p decreased with time. Additionally, hsa-miR-155-5p of B cells and hsa-miR-18b-5p of CD8+ T cells exhibited a positive correlation with miR-BHRF1-2-5P and miR-BART2-5P (0.96 ≤ r ≤ 0.99, P < 0.05). Finally, hsa-miR-181a-5p of B cells had positive correlation with miR-BART4-3p, 4-5P, 16-1, and 22 (0.97 ≤ r ≤ 0.99, P < 0.05).Our study is the first to describe the expression profile of viral and cellular miRNAs in IM caused by primary EBV infection. These results might be the basis of investigating the pathogenic mechanism of EBV-related diseases and bring new insights into their diagnosis and treatment.
Abstract Objective To more comprehensively evaluate the ability of the parameters reflecting the morphological and biomechanical properties of the cornea to distinguish clinical keratoconus (CKC) and forme fruste keratoconus (FFKC) from normal. Methods Normal eyes ( n = 50), CKC ( n = 45) and FFKC ( n = 15) were analyzed using Pentacam, Corvis ST and ORA. Stepwise logistic regression of all parameters was performed to obtain the optimal combination model capable of distinguishing CKC, FFKC from normal, named SLR1 and SLR2, respectively. Receiver operating characteristic (ROC) curves were applied to determine the predictive accuracy of the parameters and the two combination models, as described by the area under the curve (AUC). AUCs were compared using the DeLong method. Results The SLR1 model included only the TBI output by Pentacam, while the SLR2 model included the morphological parameter F.Ele.Th and two parameters from the Corvis ST, HC DfA and SP-A1. The majority of the parameters had sufficient strength to differentiate the CKC from normal corneas, even the seven separate parameters and the SLR1 model had a discrimination efficiency of 100%. The predictive accuracy of the parameters was moderate for FFKC, and the SLR2 model (0.965) presented an excellent AUC, followed by TBI, F.Ele.Th and BAD-D. Conclusion The F.Ele.Th from Pentacam was the most sensitive morphological parameter for FFKC, and the combination of F.Ele.Th, HC DfA and SP-A1 made the diagnosis of FFKC more efficient. The CRF and CH output by ORA did not improve the combined diagnosis, despite the corneal combination of morphological and biomechanical properties that optimized the diagnosis of FFKC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)