tbuckley/cabot-search huggingface dataset:
Abstract 1701: Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA
Authors: Warren Tom, Ruchi Chaudhary, Vinay Mittal, Dinesh Cyanam, Iris Casuga, Elaine Wong-Ho, Rob Bennett, Fiona Hyland, Seth Sadis, Janice Au-Young
Journal: Cancer Research (2019)

Abstract Tumor mutation burden (TMB) is a positive predictive factor for response to immune-checkpoint inhibitors in certain types of cancer. The Oncomine™ Tumor Mutation Load Assay, a 1.7Mb targeted next generation sequencing (NGS) panel, measures TMB and detects mutations in 409 cancer genes. The TMB values obtained using targeted sequencing are positively correlated with TMB measured by whole exome sequencing in NSCLC, colorectal, endometrial and gastric cancers. TMB from these tumor samples are correlated with other phenotypes associated with genomic instability, specifically microsatellite instability (MSI) and mutations involved in mismatch repair and cancer related genes. Analysis of the Oncomine™ TML Assay results with Torrent Suite and Ion Reporter software uniquely measures the degree of deamination of cytosines to uracils in fixed tissues. FFPE preservation methods can lead to significant cytosine deamination of the isolated DNA, resulting in decreased sequencing quality. In these samples, uracils are propagated as thymines and result in false C&amp;gt;T substitutions. To minimize the influence that excess deamination has on TMB results, we have incorporated a UDG enzyme treatment to eliminate damaged targets and improve usable TMB values of DNA from damaged FFPE tumor tissue. The Oncomine™ TML assay for TMB on Ion GeneStudio™ S5 in conjunction with MSI detection is informative and potentially predictive for the use of checkpoint inhibitors in multiple cancer types. Citation Format: Warren Tom, Ruchi Chaudhary, Vinay Mittal, Dinesh Cyanam, Iris Casuga, Elaine Wong-Ho, Rob Bennett, Fiona Hyland, Seth Sadis, Janice Au-Young. Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1701.
Congo sees rise in deaths from malaria, measles, and cholera as Ebola outbreak swallows up resources
Authors: Sophie Arie
Journal: BMJ (2019)

While a massive international aid operation tries to control the Ebola outbreak in the Democratic Republic of Congo (DRC), more people are dying from diseases like malaria, measles, and cholera in the same part of the country and receiving almost no assistance, the humanitarian aid charity Medecins Sans Frontieres (MSF) has said.

“People are dying because of a lack of basic services such as water, shelter, and access to healthcare,” an MSF spokesperson told The BMJ . “We have been calling on various UN agencies to scale up the assistance, but there has not been sufficient action.”

The Ebola outbreak centred in the north eastern Ituri province has killed over 1500 people since it …
Abstract 430: Prostate specific antigen (PSA) as a diagnostic and prognostic marker of prostate cancer
Authors: Ronald Simon, Martina Kluth, Kristine Fischer, Sarah Bonk, Claudia Hube-Magg, Doris Höflmayer, Maximilian Lennartz, Florian Lutz, Guido Sauter, Franziska Büscheck, Ria Uhlig, David Dum, Andreas M. Luebke, Corinna Wittmer, Frank Jacobsen, Eike Burandt, Stefan Steurer, Waldemar Wilczak, Sarah Minner
Journal: Cancer Research (2019)

Abstract Since several decades, prostate specific antigen (PSA) is regarded as a specific marker for healthy and neoplastic prostate tissues, and PSA level changes in blood and tissue are discussed as prognostic markers of prostate cancer. Using a custom-made mouse monoclonal anti-PSA antibody, we studied expression of PSA in a tissue microarray (TMAs) comprising 17,456 prostate cancers with long-term follow-up data. PSA staining was typically present in the cytoplasm and pronounced at the apical cell pole. PSA expression was often reduced (15%) or even completely lost (1%). Reduction of PSA expression was significantly linked to adverse features of prostate cancer, including advanced stage, high classical and quantitative Gleason grade, presence of lymph node metastasis, a positive surgical margin, increased cell proliferation, and reduced time to recurrence (p&amp;lt;0.0001 each). Complete lack identified a small subset of patients with the worst prognosis. There was also in impact of the subcellular localization of PSA expression: Loss of the apical staining pattern worsened the prognosis in cancers with otherwise identical levels of cytoplasmic staining. In a multivariable analysis including pT stage, Gleason grade, nodal stage, and resection margin status, loss of PSA expression proved to predict outcome independently from these parameters. Of note, PSA even stratified the prognosis of 971 cancers harboring PTEN deletions in our cancer set. In conclusion, gradual reduction of PSA staining, including a loss of the apical staining pattern, is a strong and independent prognostic marker in prostate cancer. Citation Format: Ronald Simon, Martina Kluth, Kristine Fischer, Sarah Bonk, Claudia Hube-Magg, Doris Höflmayer, Maximilian Lennartz, Florian Lutz, Guido Sauter, Franziska Büscheck, Ria Uhlig, David Dum, Andreas M. Luebke, Corinna Wittmer, Frank Jacobsen, Eike Burandt, Stefan Steurer, Waldemar Wilczak, Sarah Minner. Prostate specific antigen (PSA) as a diagnostic and prognostic marker of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 430.
Abstract 4054: Mass cytometry approaches to biomarker discovery via high-dimensional antigen-specific T cell identification and profiling
Authors: Mathew Cobbett, Michael Fehlings, Evan Newell
Journal: Cancer Research (2019)

Abstract immunoSCAPE leverages the high-dimensional immune profiling capabilities of mass cytometry combined with a unique technology for the identification of antigen-specific T-cells to support the development of immunotherapy strategies in cancer and immune-related diseases. In cancer, there is now strong evidence that immunotherapy-mediated tumor rejection can rely on tumor-specific (neoantigen-specific) CD8+ T-cells. Consequently, the discovery of neoantigens becomes valuable for personalized cancer immunotherapies. Although in silico pipelines exist, that are capable of predicting non-synonymous mutations potentially giving rise to tumor-specific neoantigens, it is not clear how accurate these methods are in identifying immunogenic and therapeutically relevant epitopes, since T-cell epitope usage can be influenced by many factors. Moreover, analysis of T-cells in cancer patients is challenging as it requires detecting rare antigen-specific T-cell populations in samples that are usually limited in volume and availability. By applying cytometry by time of flight in conjunction with combinatorial peptide-MHC tetramer staining and high-performance dimensional analysis tools, we are able to map broadly MHC-class I epitope with a high sensitivity for rare antigen-specific T-cells and perform concurrently in-depth characterization of these cells. We will show here the application of this technology in the context of immunotherapy, through the example of a murine in vivo tumor model responsive to checkpoint blockade inhibitors, as well as through the analysis of different human cancer samples. Together, by providing insights into the nature of neoantigen-specific T-cells, immunoSCAPE’s unique target discovery and high-dimensional immune profiling platform is a valuable tool for the development of novel diagnostic biomarkers and therapeutic strategies at different stages of drug development. Citation Format: Mathew Cobbett, Michael Fehlings, Evan Newell. Mass cytometry approaches to biomarker discovery via high-dimensional antigen-specific T cell identification and profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4054.
Panitumumab Alone for Maintenance Treatment in Advanced Colorectal Cancer
Authors: Gayathri Anandappa, David Cunningham
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract CT008: Tumor Treating Fields combined with radiotherapy and temzolomide for newly diagnosed glioblastoma: Final results from a pilot study
Authors: Rachel Grossman, Dror Limon, Felix Bokstein, Zvi Ram
Journal: Cancer Research (2019)

Abstract Background: Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment comprising low intensity alternating electric fields. In the Phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields significantly improved survival compared to temozolomide (TMZ). Preclinical data have demonstrated that TTFields increased glioma cell death following radiation therapy (RT), suggesting a radio-sensitizing effect of TTFields. We therefore initiated a pilot study to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by maintenance TTFields and TMZ for up to 24 months. TTFields (200kHz) were delivered for &amp;gt;18 hours/day with removal of the transducer arrays during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0. Results: Ten patients were enrolled at a single center in Israel between April and December 2017. All patients had recovered from maximal debulking surgery or biopsy. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Median age was 59 and median KPS was 80. Median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in 4 patients (40%), all of which were Grade 1-2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached. Conclusions: The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%). No other TTFields-related toxicities were reported, nor was there an increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a Phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients. Citation Format: Rachel Grossman, Dror Limon, Felix Bokstein, Zvi Ram. Tumor Treating Fields combined with radiotherapy and temzolomide for newly diagnosed glioblastoma: Final results from a pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT008.
Post-transplant lymphoproliferative disorder-related admissions in the United States.
Authors: Arlene Yu, Prakash Acharya, Seema Singh, Momcilo Durdevic, Andreea Stan, Abhishek Nimkar, Henrik Elenius, Stephen Jesmajian, Ashutossh Naaraayan
Journal: Journal of Clinical Oncology (2019)

e19071 Background: Post-transplant lymphoproliferative disorders (PTLD) is an immunosuppression-related malignancy complicating solid organ transplant (SOT) and non-solid organ transplant (NSOT) (peripheral stem cell and bone marrow transplant). The epidemiology of PTLD-related hospital admissions (PRA) is unclear. The objective of our study is to describe the trend and outcomes of PRA in the United States. Methods: A descriptive, retrospective study was conducted using the National Inpatient Sample database from 2009-2014. PRA were selected using International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis code (238.77). Multivariate regression analysis was performed to determine mortality and length of stay (LOS) in PRA. Results: The incidence of PRA in transplant-related hospital admissions was 7.19 per thousand admissions (pta) in 2009 and 7.24 pta in 2014 with annual percentage change (APC) of 0.1% (p = 0.9). The median age of patients with PRA was 47 (25-75 percentile: 19-61) years, 38.8% were females, 69.9% were white and 10.7% were African-American. Among patients with PRA, 91.1% had SOT [kidney (31.4%), liver (20.9%), heart (14.6%), lung (7%) and small intestines (1.89%)]; 7.1% had NSOT [bone marrow (3.9%) and peripheral stem cell (2%)] and 1.8% had two or more organ transplants. The most common principal diagnosis in PRA were complications of organ transplant (33.3%), encounter for anti-neoplastic chemotherapy (11.4%), neutropenia (5%), acute kidney injury (3.7%) and hearing loss (1.7%). Among transplant-related hospital admissions, PRA had higher adjusted odds of inpatient mortality [Odds ratio (OR) 2.57 (Confidence Interval (CI) 1.69-2.42), p &lt; 0.001] and longer LOS [4.22 days (CI 3.26-5.17), p &lt; 0.001] than non-PRA. Among PRA, those with NSOT have higher adjusted odds of mortality [OR 2.98 (CI 1.07-8.29), p = 0.036] and longer LOS [16.27 days (CI 3.51-29.03), p &lt; 0.013] compared to those with SOT. Conclusions: PRA have higher odds of mortality and longer LOS compared to other transplant-related hospital admissions. Even though SOT accounts for most of the PRA, the adjusted odds of mortality are significantly higher in PRA with NSOT.
Changes in Perceptions of Discrimination in Health Care in California, 2003 to 2017
Authors: Lucy B. Schulson, Michael K. Paasche-Orlow, Ziming Xuan, Alicia Fernandez
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Research in the early 2000s in California demonstrated that racial and ethnic minorities, immigrants, and those with limited English proficiency (LEP) experienced high rates of discrimination in health care. Less is known about how patients' perceptions of discrimination in health care have changed since then. <h3>Objective</h3> To determine whether perceptions of discrimination in health care have changed overall and for specific vulnerable populations. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the California Health Interview Survey for state residents aged 18 years and older for 2 periods, 2003 to 2005 and 2015 to 2017. χ<sup>2</sup>analyses and multivariate logistic regression were performed to compare recent discrimination in health care in late vs early periods controlling for race/ethnicity, poverty level, education, insurance status, usual source of care, self-reported health, and LEP. Additional subanalyses were performed by race/ethnicity, immigrant status, and LEP status. Jackknife replicate weights were provided by the California Health Interview Survey. <h3>Exposure</h3> Survey year was dichotomized as combined 2003 to 2005 and combined 2015 to 2017. <h3>Main Outcomes and Measures</h3> Survey respondents were identified as having experienced recent discrimination in health care if they responded "yes" to the question, "Was there ever a time when you would have gotten better medical care if you had belonged to a different race or ethnic group?" and reported that this occurred within the last 5 years. <h3>Results</h3> There were 84 088 participants in 2003 to 2005 (51.0% female; 14.7% aged ≥65 years) and 63 242 participants in 2015 to 2017 (51.1% female; 18.0% aged ≥65 years). Rates of recent discrimination in health care decreased from 6.0% to 4.0% (difference, 2.0%; 95% CI, 1.5%-2.5%;<i>P</i> &lt; .001). In adjusted analyses, perceptions of discrimination in health care decreased in 2015 to 2017 compared with 2003 to 2005 (odds ratio [OR], 0.60; 95% CI, 0.53-0.68;<i>P</i> &lt; .001). There was a significant race × period interaction for Latino individuals (OR, 0.58; 95% CI, 0.40-0.83;<i>P</i> = .003) but not for Asian individuals (OR, 0.76; 95% CI, 0.50-1.16;<i>P</i> = .20) or African American individuals (OR, 1.24; 95% CI, 0.76-2.02;<i>P</i> = .40). There was a significant immigrant status × period interaction (OR, 0.55; 95% CI, 0.44-0.69;<i>P</i> &lt; .001) and LEP status × period interaction (OR, 0.67; 95% CI, 0.51-0.89;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This study suggests that perceptions of discrimination in health care in California decreased between 2003 to 2005 and 2015 to 2017 among Latino individuals, immigrants, and those with LEP. African American participants reported consistently high rates of discrimination, indicating that interventions targeting health care discrimination are still necessary.
Abstract 2488: CellMinerCDB and CellMiner web-applications for genomics and pharmacogenomics analyses of cancer cell lines
Authors: William C. Reinhold, Sudir Varma, Yang-Hsin Wang, Fathi Elloumi, Yves Pommier
Journal: Cancer Research (2019)

Abstract The CellMiner (http://discover.nci.nih.gov/cellminer)and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-applications provide complimentary functionality and datatsets that may be used for comparisons of genomic, molecular and pharmacological data within the NCI-60 cancerous cell lines, Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC), Cancer Therapeutics Response Portal (CTRP), NCI/DTP small cell lung cancer (SCLC), and NCI Almanac cell line sets. CellMiner contains data for the NCI-60, including the most extensive sets of molecular and drug activity data (generated by the NCI Developmental Therapeutics Program https://dtp.cancer.gov),found for any of the databases. CellMinerCDB contains all the above mentioned cell line sets, including the substantially increased cell line numbers and tissue of origin types found in the CCLE, GDSC, and CTRP. The two web-applications have separate but complimentary functionalities. Each cell line set has some variable number of data types, some of which measure the same parameters, and some that do not. The number and make up of cell lines also varies, from 60 for the NCI-60, 69 for the SCLC, and ~1000 for the CCLE, GDSC, and CTRP. As there are partial overlaps of cell lines between many of these cell line sets, one may fill in some data type gaps by merging data from two sources, as well as do quality control by comparisons of the same data from multiple institutions. This rich set of data and functions facilitates the exploration of the relationships between and among molecular alterations and pharmacological responses in cancer cell lines from the omic perspective. Citation Format: William C. Reinhold, Sudir Varma, Yang-Hsin Wang, Fathi Elloumi, Yves Pommier. CellMinerCDB and CellMiner web-applications for genomics and pharmacogenomics analyses of cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2488.
Abstract 5262: Lipidomic profiling of neuroblastoma cells after treatment with novel withalongolide A 4, 19, 27-triacetate (WGA-TA)
Authors: Chitra Subramanian, Rajendiran Thekkelnaycke, Tanu Soni, Valerie P. Opipari, Barbara N. Timmermann, Mark S. Cohen
Journal: Cancer Research (2019)

Abstract Introduction: Neuroblastoma (NB) is a pediatric solid tumor that affects approximately 700 children every year in the United States. Despite advances in treatment, the cure rate for high risk advanced NB having N-myc amplification has a poor response of 40-50%. Standard of care treatment for high risk NB patient consists of surgery, intensive chemotherapy and radiotherapy. Recently, we and others have shown that withanolide treatment of NB induce apoptosis of NB cells, through several mechanism including lipid oxidation, down regulation of N-myc and suppression of Akt/mTOR/NF-κB activation. Therefore, we hypothesized that mass spectrometric analysis of untargeted lipidomic profiling after treatment of NB cells with withanolide WGA-TA will identify novel prognostic and diagnostic biomarkers of NB. Methods: Validated neuroblastoma cell lines IMR32 (N-myc amplified) and SH-EP (N-myc non-amplified) were grown in 2D culture in appropriate growth medium. Lipids were extracted from cells using modified Bligh and Dyer method. Lipidomic profiling was carried out using LC MS/MS. Principal component analysis (PCA) was used to identify differentially regulated metabolites. Results: Principal component analysis of NB cell lines and WGA-TA treatment showed complete separation of samples as well as internal controls. Initial analysis of lipid profiling of IMR32 and SH-EP cells showed differential regulation of several lipids. N-myc non-amplified SH-EP cells have upregulation of phospholipids such as phosphocholine (PC), phosphor ethanol amine (PE), sphingomyelin (SM) and free fatty acid, whereas glycerol lipid diacyl glycerol (DG) is down regulated in SH-EP cells compared to IMR32 cells. Treatment of IMR32 cells with WGA-TA led to up regulation of phospho lipids such as PC, phosphoserine (PS), SM, Lyso PE, free fatty acids just like N-myc non-amplified cells. But, triglycerides (TG) were up regulated after treatment with WGA-TA in both IMR32 and SH-EP cells. Conclusions: WGA-TA treatment of N-myc amplified cells led to upregulation of phospholipids similar to that of N-myc non-amplified cells indicating that CDP-Choline pathway lipids might play an important role in NB. Further analysis is needed to unravel the link between N-myc and lipid metabolism in NB. Citation Format: Chitra Subramanian, Rajendiran Thekkelnaycke, Tanu Soni, Valerie P. Opipari, Barbara N. Timmermann, Mark S. Cohen. Lipidomic profiling of neuroblastoma cells after treatment with novel withalongolide A 4, 19, 27-triacetate (WGA-TA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5262.