896: Artificial Intelligence Re-Analysis of Gene Array Data Identifies Novel Markers of Urothelial Cancer Progression

2007 ◽  
Vol 177 (4S) ◽  
pp. 297-298
Author(s):  
James W. Catto ◽  
Maysam F. Abbod ◽  
Derek Linkens ◽  
Peter J. Wild ◽  
Alexander Herr ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 827
Author(s):  
Yiqiao Luo ◽  
Bin Yan ◽  
Li Liu ◽  
Libo Yin ◽  
Huihui Ji ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and the therapeutic options available usually have little impact on survival. Great hope is placed on new therapeutic targets, including long noncoding RNAs (lncRNAs), and on the development of new drugs, based on e.g., broccoli-derived sulforaphane, which meanwhile has shown promise in pilot studies in patients. We examined whether sulforaphane interferes with lncRNA signaling and analyzed five PDAC and two nonmalignant cell lines, patient tissues (n = 30), and online patient data (n = 350). RT-qPCR, Western blotting, MTT, colony formation, transwell and wound healing assays; gene array analysis; bioinformatics; in situ hybridization; immunohistochemistry and xenotransplantation were used. Sulforaphane regulated the expression of all of five examined lncRNAs, but basal expression, biological function and inhibition of H19 were of highest significance. H19 siRNA prevented colony formation, migration, invasion and Smad2 phosphorylation. We identified 103 common sulforaphane- and H19-related target genes and focused to the virus-induced tumor promoter APOBEC3G. APOBEC3G siRNA mimicked the previously observed H19 and sulforaphane effects. In vivo, sulforaphane- or H19 or APOBEC3G siRNAs led to significantly smaller tumor xenografts with reduced expression of Ki67, APOBEC3G and phospho-Smad2. Together, we identified APOBEC3G as H19 target, and both are inhibited by sulforaphane in prevention of PDAC progression.


2016 ◽  
Vol 5 ◽  
pp. e366 ◽  
Author(s):  
Gyöngyi Munkácsy ◽  
Zsófia Sztupinszki ◽  
Péter Herman ◽  
Bence Bán ◽  
Zsófia Pénzváltó ◽  
...  

2016 ◽  
Author(s):  
Joshua Mannheimer ◽  
Jared S. Fowles ◽  
Katherine Shaumberg ◽  
Dawn L. Duval ◽  
Ashok Prasad ◽  
...  

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 486-486
Author(s):  
Takahiro Yoneyama ◽  
Hirotake Kodama ◽  
Shogo Hosogoe ◽  
Ayumu Kusaka ◽  
Noriko Tokui ◽  
...  

486 Background: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and September 2017. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m2. Mean observation period was 28.7 (3–111) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the ovearall survival were 22.0 months in the BChE > 168 U/L group and 11.0 months in the BChE < 168 group (p = 0.0035). The level of serum BChE showed no association with treatment effect. Conclusions: Serum BChE level before chemotherapy may have the potential to predict overall survival in patients with advanced upper-tract urothelial cancer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16008-e16008
Author(s):  
Nikola Kaludov ◽  
Mohummad Minhaj Siddiqui ◽  
Max Kates ◽  
Hemantkumar Tripathi ◽  
Amatul Nasir Salma ◽  
...  

e16008 Background: Urine tests such as urine cytology are commonly used for the diagnosis and monitoring of urothelial cancer. These tests are often limited by issues related to sensitivity or specificity. It is well known that derangement of cellular metabolism is one of the hallmarks of carcinogenesis. As urothelial cancer is in constant contact with urine, we hypothesize that metabolite composition in the urine may provide insight into possible urothelial cancer presence in the urinary tract. In this study, we evaluated a metabolomics based urine test for the detection of urothelial cancer. Methods: In this prospective, multi-institutional IRB approved study, urine samples were collected from a total of 57 urothelial cancer patients and non-urothelial cancer controls. Gas chromatography profiles of urine small molecule metabolites were generated to yield over 2400 data points of metabolite peaks and troughs for every urine sample. A machine-learning based algorithm (Abilis Life Sciences) was constructed to predict urothelial cancer versus non-cancer controls through analysis of peaks and trough patterns of urine metabolomics profiles. Predictions were made in a blinded fashion and descriptive statistics of test sensitivity and specificity were generated. Results: The urine metabolite composition of 57 patients were analyzed and urothelial cancer predictions were generated. The test demonstrated an overall accuracy of 89.5% (51 out of 57 cases correctly predicted). The sensitivity of the test was 97.1% (34 out of 35) and specificity was 77.3% (17 out of 22). The Positive Predictive Value is 87.2%, while the Negative Predictive Value is 94.4%. The area under the curve for the receiver operating characteristic curve was 0.87. Conclusions: Urine based metabolic profile analysis using artificial intelligence algorithms is a promising potential diagnostic test for detection of urothelial cancer. Further testing is ongoing to increase robustness of the validation.


2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Stefan Kurtenbach ◽  
Sarah Kurtenbach ◽  
Georg Zoidl

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Carlotta Raschioni ◽  
Giulia Bottai ◽  
Andrea Sagona ◽  
Valentina Errico ◽  
Alberto Testori ◽  
...  

Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 (p=3.28E−02) and CD163 (p=6.92E−03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.


Sign in / Sign up

Export Citation Format

Share Document