ABSTRACT: This cohort included 118 consecutive and unselected patients who underwent, between September 1998 and September 2010, curative intent surgery for PDA (Brussels Dataset). Archived tumor specimens were available for the entire study population. Exclusion criteria included: preoperative chemotherapy or chemoradiotherapy (n=12), macroscopically incomplete resection (R2) (n=6), or tumor histology other than ductal adenocarcinoma (n=19). We also excluded patients who died of postoperative complications within 30 days following surgery (n=1) because they are non-informative for this kind of translational study.
Project description:10x sequencing of TSPAN8+, GP2+ or Unselected medullary thymic epithelial cells (mTEC) isolated from female C57BL/6, BALB/c, and C57BL/6 x BALB/c F1 mice with the intent to identify co-expression patterns in promiscuously expressed genes in individual mTEC.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify mRNA markers for ESCC CRT-response prediction through gene expression analyses.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses.
Project description:The study aim to briefly profile miRNA expression differences in hypopharyngeal carcinoma patients, who underwent surgery and chemoradiotherapy, with different survival status. We applied Agilent microRNA microarray to FFPE samples from 8 patients with hypopharyngeal carcinoma.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patientsM-bM-^@M-^Y survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify mRNA markers for ESCC CRT-response prediction through gene expression analyses. Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery and 10 normal esophageal epithelia using Affymetrix U133 Plus 2.0 arrays.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses. MiRNA expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery using Agilent human miRNA microarrays based on miRBase (release 18.0) GeneChip®.
Project description:Acantholytic squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). Response to standard chemoradiotherapy (CRT) varies considerably. A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. Patients with histologically confirmed, localized ASCC, treated between 1998 and 2019 at three different sites (Frankfurt, Berlin, Tübingen) of the German Cancer Consortium (DKTK) were included. All patients received 5-FU/MMC-based CRT. Patient cohorts for molecular analysis were defined based on availability and quality of samples, including baseline formalin fixed paraffin embedded biopsies for immunohistochemistry (n=130), baseline RNA sequencing (n=98), peripheral blood immune profiling by sequential multiparametric flow cytometry (n=47), and serum cytokine multiplex assays measurement (n=35). Tumor response, freedom from locoregional failure (FFLF), and freedom from distant metastasis (FFDM) were correlated with clinicopathologic and molecular findings.
Project description:A total of 97 LARC patients treated at the Institute for Oncology and Radiology of Serbia in the period of 2018-2019 were included in the study. Patients were treated with long-course chemoradiotherapy (CRT): Radiotherapy (RT) was delivered with a total dose of 50.4 Gy in 28 fractions; concomitant chemotherapy (5-FU, 350 mg/m2 daily) and Leucovorin (25 mg/m2 daily) was administered during the first and the fifth week of RT. Patients were evaluated in week 6-8 after treatment completion with pelvic MRI scan and rigid proctoscopy. Pathohistological response after surgery was assessed according to tumor regression grading (TRG) categories by Mandard. Twenty biopsy samples taken at diagnosis were used for proteomic analysis, 9 responders (R, TRG 1-2), and 11 non-responders (NR, TRG 3-5), in order to achieve the maximum range of different molecular features potentially associated with response.
Project description:Objectives: Secretion of extracellular vesicles (EV) and associated micro-RNAs (miR) is altered during cellular stress and may serve as biomarkers of organ injury. We hypothesized that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. Design: Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial Setting: Single center ICU between September 2015 and September 2018 Interventions: Intravenous sildenafil citrate 12.5 mg kg-1 over 150 min or dextrose 5% at the commencement of surgery. Measurements and main results: Urine samples were collected before and 24 hours after the procedure from 93 cardiac surgery patients. Urine EV concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced to detect differentially expressed miR. Verification was performed with advanced TaqMan assays in samples from all patients. Urine EV concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for aquaporin-2 and β1-integrin also increasing. Pre surgery podocalyxin-positive EV were significantly lower, and β1-integrin EV werehigher in patients with AKI. The levels of the former correlated with the severity of theinjury. miR-125a-5p was expressed at higher levels in urine from patients with AKI stage 2/3. Levels of miR-10a-5p decreased after surgery in AKI patients; its levels correlated with the severity of the injury. Preoperative levels of podocalyxin EVs and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 80.9%) AKI prediction. Conclusions: Lower levels of podocalyxin-positive EV at baseline predict the severity of post-surgery AKI. Urine EV concentrations and miR expression offer excellent predictive accuracy when combined with commonly measured biomarkers.
Project description:Purpose/Objective(s): To correlate gene expression and overall survival (OS) in patients with pancreatic adenocarcinoma who have undergone definitive surgery Materials/Methods: Patients were identified that were treated with definitive surgery without neoadjuvant and adjuvant therapy for pancreatic adenocarcinoma. The Beaumont BioBank consented patients then collected and stored tissue samples. Patients were grouped into short term (<10 months, n=13) and long term (>20 months, n=11) survivors. RNA was extracted from fresh frozen tissues, and global gene expression patterns in the short and longer-term survivors were compared. Pathway analysis of the significant genes was also performed. Results: The median age at the time of surgery was 64 years. The mean overall survival in each group was 7.5 months and 32.0 months. We identified 163 genes that were differentially expressed between patients who survived <10 months and >20 months from their definitive surgery. Many of the genes identified have known prognostic importance in oncology; however, less than half of these genes have been reported to be associated with survival in pancreatic adenocarcinoma. Pathway analysis identified expression targets of SP1, JUN, and EGF to be highly regulated based upon differences in overall survival. Conclusions: In pancreatic adenocarcinoma patients who have undergone definitive resection, we have identified multiple genes associated with inferior survival. Many of the genes reported in this study have not previously been linked to overall survival in this patient population.