tbuckley/cabot-search huggingface dataset:
Validation of the prognostic value of NF-κB p65 in prostate cancer: A retrospective study using a large multi-institutional cohort of the Canadian Prostate Cancer Biomarker Network
Authors: Andrée-Anne Grosset, Véronique Ouellet, Christine Caron, Gabriela Fragoso, Véronique Barrès, Nathalie Delvoye, Mathieu Latour, Armen Aprikian, Alain Bergeron, Simone Chevalier, Ladan Fazli, Neil Fleshner, Martin Gleave, Pierre Karakiewicz, Louis Lacombe, Jean-Baptiste Lattouf, Theodorus van der Kwast, Dominique Trudel, Anne-Marie Mes-Masson, Fred Saad
Journal: PLoS Medicine (2019)

Background The identification of patients with high-risk prostate cancer (PC) is a major challenge for clinicians, and the improvement of current prognostic parameters is an unmet clinical need. We and others have identified an association between the nuclear localization of NF-κB p65 and biochemical recurrence (BCR) in PC in small and/or single-centre cohorts of patients. Methods and findings In this study, we accessed 2 different multi-centre tissue microarrays (TMAs) representing cohorts of patients (Test-TMA and Validation-TMA series) of the Canadian Prostate Cancer Biomarker Network (CPCBN) to validate the association between p65 nuclear frequency and PC outcomes. Immunohistochemical staining of p65 was performed on the Test-TMA and Validation-TMA series, which include PC tissues from patients treated by first-line radical prostatectomy (n = 250 and n = 1,262, respectively). Two independent observers evaluated the p65 nuclear frequency in digital images of cancer tissue and benign adjacent gland tissue. Kaplan–Meier curves coupled with a log-rank test and univariate and multivariate Cox regression models were used for statistical analyses of continuous values and dichotomized data (cutoff of 3%). Multivariate analysis of the Validation-TMA cohort showed that p65 nuclear frequency in cancer cells was an independent predictor of BCR using continuous (hazard ratio [HR] 1.02 [95% CI 1.00–1.03], p = 0.004) and dichotomized data (HR 1.33 [95% CI 1.09–1.62], p = 0.005). Using a cutoff of 3%, we found that this biomarker was also associated with the development of bone metastases (HR 1.82 [95% CI 1.05–3.16], p = 0.033) and PC-specific mortality (HR 2.63 [95% CI 1.30–5.31], p = 0.004), independent of clinical parameters. BCR-free survival, bone-metastasis-free survival, and PC-specific survival were shorter for patients with higher p65 nuclear frequency (p < 0.005). As the small cores on TMAs are a limitation of the study, a backward validation of whole PC tissue section will be necessary for the implementation of p65 nuclear frequency as a PC biomarker in the clinical workflow. Conclusions We report the first study using the pan-Canadian multi-centre cohorts of CPCBN and validate the association between increased frequency of nuclear p65 frequency and a risk of disease progression.
Abstract 1242: Examining the role of heme and respiratory proteins in the progression of KRAS/LKB1 mutant subtype
Authors: Sanchareeka Dey, Sarada Preeta Kalainayakan, Poorva Ghosh
Journal: Cancer Research (2019)

Abstract Currently there are few successful targeted therapies for non-small cell lung cancer (NSCLC). Targeting mutations in EGFR, BRAF, ALK etc. provide treatment options only for a defined subset of adenocarcinoma patients leaving majority of adenocarcinoma and squamous carcinoma patients without any options. Activating KRAS mutations are found in 15-30% of all NSCLC patients; however, existing treatment options for KRAS-mutant cancer are not effective in the subset with concomitant loss of LKB1 (kinase that phosphorylates AMPK). Several studies demonstrate the importance of mitochondrial metabolism and oxidative phosphorylation (OXPHOS) in lung tumorigenesis. Components of OXPHOS complexes and markers of mitochondrial biogenesis are highly predictive of reduced overall survival in NSCLC patients. A study using genetically engineered mouse models (GEMMs) for lung cancer (KrasLSLG12D/+Trp53-/- and KrasLSL-G12D/+Lkb1-/-) showed that along with glucose, lactate contributes to the TCA cycle. This highlights the importance of OXPHOS in these models. Also, heme is a prosthetic group for several of these OXPHOS proteins and is involved in oxygen transport and utilization. Hence, we aim to investigate unique therapeutic targets by examining the role of heme and respiratory proteins in the progression of KRAS/LKB1 mutant subtype. We used LSL-KrasG12D LKB1-/- (LSL-KRASG12D; LKBloxP/loxP; LSL-Luciferase (KLLuc)) GEMM model for our study. Briefly, the mice were infected with AdenoCre virus, and sacrificed at different intervals in the progression of the tumors. For histological and immunohistochemical analysis, lung tissues were formalin fixed, paraffin embedded and sectioned (5µm thick). H&amp;E staining showed consistent progression in tumor size over time. We will examine the time-course expression of OXPHOS, heme pathway proteins, and hemoproteins to determine the extent to which this lung tumor subtype depends on heme and respiratory proteins for its progression. Citation Format: Sanchareeka Dey, Sarada Preeta Kalainayakan, Poorva Ghosh. Examining the role of heme and respiratory proteins in the progression of KRAS/LKB1 mutant subtype [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 1242.
Abstract 3303: Development and initial validation of a prognostic score based on structured data from EHRs
Authors: Daniel Backenroth, Josh D. Haimson, Neal J. Meropol, Shrujal S. Baxi
Journal: Cancer Research (2019)

Abstract Introduction Real world data (RWD) is increasingly used to supplement clinical trial data. Prognostic scores (PS) such as ECOG performance status (ECOG) are important for matching patient populations and assessing treatment impact, yet such PS are often missing from patient records or are embedded in physician narratives. An accurate PS that does not rely on physician assessment or data entry would have broad utility. We therefore undertook development of a PS based solely on structured data from RWD across numerous cancer diagnoses (the structured PS). We then sought initial validation of the structured PS in patients treated with checkpoint inhibitors (CIT). Methods Using the Flatiron Health electronic health record-derived database, we applied LASSO regression to develop the structured PS to predict for overall survival (OS) after starting any first-line (1L) cancer therapy. Data included laboratory values and vital signs from between 30 days before and 15 days after start of treatment as well as age. The structured PS was developed from ~39K patients with multiple myeloma, chronic lymphocytic leukemia or one of 8 solid tumor malignancies. We evaluated the structured PS using concordance, i.e., how often the score correctly predicts the relative OS of two randomly selected patients, on ~24K patients, comparing to a baseline based on age and ECOG, when available. We then measured the association of OS with the structured PS at start of 1L CIT in patients with five tumor types where 1L CIT is common. Results The concordance of the structured PS was 66%-73%, on average 6% higher than that of age and ECOG. Table 1 shows by cancer type # of patients and median OS from 1L CIT for quartiles of the structured PS (NR=not reached). Conclusion A structured PS can be an important pan-tumor variable in investigations of OS using RWD, including for patients treated with first-line CIT. OS from 1L CIT by quartiles of structured PSDiseasenQ1 median (95% CI) in monthsQ2 median (95% CI) in monthsQ3 median (95% CI) in monthsQ4 median (95% CI in months)Head and neck3704 (3-5)9 (7-12)14 (12-Inf)NR (NR-Inf)Melanoma16355 (4-6)20 (15-26)33 (22-Inf)NR (NR-Inf)Non-small cell lung cancer41714 (3-4)9 (8-10)14 (13-16)24 (21-29)Renal cell carcinoma2775 (3-7)23 (12-Inf)20 (13-Inf)NR (28-Inf)Urothelial cancer6122 (2-3)6 (4-7)9 (7-13)NR (15-Inf) Note: This abstract was not presented at the meeting. Citation Format: Daniel Backenroth, Josh D. Haimson, Neal J. Meropol, Shrujal S. Baxi. Development and initial validation of a prognostic score based on structured data from EHRs [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 3303.
Looking Forward, Not Backward, on Watch and Wait for Rectal Cancer
Authors: Fahima Dossa, Sarah E. Moore, Nancy N. Baxter
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
Positive Predictive Values and Potential Success of Suicide Prediction Models
Authors: Bridget B. Matarazzo, Lisa A. Brenner, Mark A. Reger
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Abstract 09: Ultra-Fast Hypothermia Inhibit Early Cerebral Consumption of Lactate After Experimental Cardiac Arrest in Rabbits : A Microdialysis Study
Authors: Matthias Kohlhauer, Alexandra Demelos, Emilie Boissady, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2018)

Introduction: Ultra-fast hypothermia through total liquid ventilation (TLV) has been shown to be neuroprotective after cardiac arrest. Hypothesis: The mechanism could involve a modification in brain metabolic substrat. Method: Anesthetized rabbits were instrumented with a carotid flow probe as well as arterial and jugular venous catheters. A microdialysis catether was implanted in the right brain cortex. Animals were then submitted to 10 min of ventricular fibrillation and cardiopulmonary resuscitation. After resumption of spontaneous circulation (ROSC), they were randomly submitted to ultra-fast cooling to 32°C by TLV (TLV group) or normothermic follow-up (Control) during 4h. Cerebral consumption of lactate, glucose and O 2 was calculated using arteriovenous differences in their content times mean carotid blood flow. Results: In Control, cerebral blood flow was significantly and sustainly decreased after ROSC (61±6 vs 101±6 ml/min after 240 min vs baseline), with a further decrease with hypothermia in TLV group (23±2 ml/min after 240 min, p&lt;0.05). As compared to Control, TLV reduced the cerebral consumption of glucose (-69% at 240 min) and O 2 (-73% at 240 min). Importantly, Control animals showed a dramatic but transient cerebral consumption of lactate during the first 120 min after cardiac arrest (e.g. 124±31 mmol/min at 60 min). Concomitantly, this was associated with an increase in pyruvate extracellular stocks in brain (e.g. 57±10 μmol/L at 30 min). In TLV group, hypothermia blunted this initial burst of lactate consumption (e.g. 41±12 mmol/min at 60 min, p&lt;0,05) and led to an accumulation in extracellular lactate ( e.g. 2053±68 vs 1246±278 μmol/L at 60 min, in TLV and Control respectively). This early build-up of lactate was then progressively consumed after 120 min in TLV group, allowing a delayed accumulation in pyruvate extracellular stocks from 120 min until the end of follow-up (103±19 and 17±4 μmol/L of pyruvate at 240 min in TLV vs Control respectively). Conclusion: Ultra-fast hypothermia reduces the cerebral consumption of lactate during the first 120 min after ROSC, allowing a delayed renewal in pyruvate stocks. This could explain the potent benefit of hypothermia during this early therapeutic window of 120 min.
Clinical and Therapeutic Implications of Cancer Stem Cells
Authors: Michael F. Clarke
Journal: New England Journal of Medicine (2019)

Interview with Dr. Michael F. Clarke on clinical and therapeutic implications of cancer stem cells. (09:15)Download Cancers arise in tissues that can replicate and self-renew. Like normal tissues, cancers can replenish themselves, grow, and metastasize because of stem cells that are similar to normal stem cells but seem to respond less well to environmental stop signals in their niche. Therapy that targets cancer stem cells may be the next avenue of cancer treatment.
Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy
Authors: Seung Up Kim, Yeon Seok Seo, Han Ah Lee, Mi Na Kim, Eun Hwa Kim, Ha Yan Kim, Yu Rim Lee, Hye Won Lee, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seong Gyu Hwang, Kyu Sung Rim, Soon Ho Um, Won Young Tak, Young Oh Kweon, Beom Kyung Kim, Soo Young Park
Journal: Clinical Gastroenterology and Hepatology (2019)
A phase 2 study of capecitabine plus oxaliplatin therapy (XELOX) for patients with inoperable/advanced gastric cancer who were resistant/intolerable to fluoropyrimidine, CDDP, taxane, and CPT-11 (OGSG1403)
Authors: J. Kawada, N. Sugimoto, T. Hirokazu, S. Ueda, K. Murakami, K. Nishikawa, Y. Kurokawa, K. Fujitani, H. Kawakami, D. Sakai, T. Shimokawa, T. Satoh
Journal: Annals of Oncology (2019)
Abstract 5068: Genomic regulation of the cell cycle as a function of ARID1A occupancy in breast epithelial cells
Authors: Sham Jdeed, Balint L. Balint, Iván P. Uray
Journal: Cancer Research (2019)

Abstract The idea of chemoprevention introduced a new concept both in clinical practice and experimental approaches. While single agent ER-independent chemopreventive therapy based on RXR-selective retinoids and other agents has produced promising results, even minor toxicity remains an obstacle to their clinical use. We performed unbiased high throughput screening to identify synergistic growth suppressive combinations of agents in normal mammary epithelial cells. A RXR-selective agonist and a beta-adrenergic inhibitor, as a candidate combination, at low concentrations demonstrated marked cancer preventive activity in a mouse model of Her2-induced ER-negative breast cancer. To elucidate the molecular mechanisms of this chemopreventive activity proteomic analyses of the candidate drug combination ensued. These revealed increased levels and phosphorylation of the DNA damage sensor ATM, along with elevated levels of the ARID1A subunit of the SWI/SNF chromatin remodeler in normal breast epithelial cells, but not in in situ breast carcinoma cells. Thus, we hypothesized that the maintenance of genomic integrity through ARID1A is a critical factor in the effectiveness of cancer preventive agents and helps reduce the odds of transformation. Genomic regions of increased accessibility are mapped by high throughput sequencing enabling multidimensional assays of the regulatory chromatin regions. Enhancers identified through chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) for H3K27 acetyl complemented with histones H3K4 will be discussed. We propose that ARID1A may mediate antiproliferative effects through genome-wide pausing of transcription of cell cycle regulatory genes. These results will help establish a role for the crosstalk of rexinoid and adrenergic signaling in the maintenance of a conserved chromatin remodeling mechanism and thus, premalignancy in breast epithelial cells. Citation Format: Sham Jdeed, Balint L. Balint, Iván P. Uray. Genomic regulation of the cell cycle as a function of ARID1A occupancy in breast epithelial cells [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 5068.
Time-staggered delivery of erlotinib and doxorubicin by gold nanocages with two smart polymers for reprogrammable release and synergistic with photothermal therapy
Authors: Yanlin Feng, Yan Cheng, Yun Chang, Hui Jian, Runxiao Zheng, Xiaqing Wu, Keqiang Xu, Li Wang, Xiaomin Ma, Xi Li, Haiyuan Zhang
Journal: Biomaterials (2019)
Efficacy and safety of early administration of pegfilgrastim in patients with esophageal cancer treated by docetaxel, cisplatin, and 5-fluorouracil (DCF): a phase 2 prospective study
Authors: T. Ishikawa, T. Yasuda, T. Okayama, H. Konishi, Y. Naito, T. Taguchi, Y. Itoh
Journal: Annals of Oncology (2019)
Abstract 19506: The Role of Mir-16 on Endothelial Dysfunction in Rat with Atherosclerotic Diet with a Chronic Model of Femoral Artery Occlusion and Carotid Balloon Injury
Authors: Sabato Sorrentino, Alberto Polimeni, Claudio Iaconetti, Jolanda Sabatino, Clarice Gareri, Francesco Passafaro, Maria Colangelo, Caterina Covello, Filomena Caria, Alessandra Carvelli, Mariella Miceli, Salvatore Giampà, Antonio Curcio, Salvatore De Rosa, Ciro Indolfi
Journal: Circulation (2012)

Background: Peripheral artery disease (PAD) is associated to coronary endothelial dysfunction and is an important predictor of future cardiovascular events. MicroRNAs play a critical role in modulating a variety of cellular processes by post-transcriptional regulation of their target genes. They are highly expressed in human endothelial cells (ECs), playing key role in essential biological processes. Thus, the aim of the present study was to evaluate the role, if any, of miRNAs in endothelial dysfunction in a model of PAD. Methods and Results: Male Wistar rats were provided of a standard atherogenic, high cholesterol diet and divided into 4 groups: no treatment (sham); rat subjected to vascular injury by balloon catheter (B.I.); rats underwent common femoral artery ligation (PAD); rats subjected to common femoral artery ligation and, after 21 days, subject to balloon injury (PAD+B.I.). RNA from intima was separately obtained from carotid arteries and evaluated for endothelial specific miRNAs using a stem-loop real-time-PCR. Interestingly, among the most important miRNAs expressed, real time RT-PCR showed an important up-regulation of miR-16 in ECs extracted by injured carotid artery of PAD+BI group respect the ECs of the others groups. A bioinformatics approach revealed highly conserved binding sites for miR-16 in the 3’UTR of SMAD7, an inhibitor of TGF-β1 signaling. The expression level of SMAD7 was measured in ECs treated with antagomiR-16 using immunoblotting analysis. Up-regulation of miR-16 revealed a reduction of SMAD7 levels. Also, we evaluated the effects of miR-16 inhibition in ECs on mRNA and protein levels of eNOS and NF-kB, regulators of endothelial dysfunction. Real-time PCR showed an increased expression of eNOS mRNA in ECs treated with antagomiR-16. Furthermore, immunoblotting revealed increased eNOS protein production as well as its activation in ECs by miR-16 inhibition. Finally, we showed an increased NF-kB activation in ECs after up-regulation of miR-16. Conclusions: Our data demonstrated that in rat with PAD and atherosclerotic diet, miR-16 is up-regulated in endothelial cell of carotid arteries after balloon injury. This findings might of importance to assess future strategies in patients with PAD.
Ebola: Epidemic in DRC is one of world’s “most complex health emergencies”
Authors: Alison Shepherd
Journal: BMJ (2019)

Reuters

Family members and healthcare workers gather for the funeral of a baby killed by Ebola in Beni, a town in the North Kivu province of the Democratic Republic of the Congo.

The outbreak, with more than 2100 cases and more than 1412 confirmed deaths in …
Abstract 16954: Should We Perform Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Obstructive Sleep Apnea? A Nationwide Inpatient Sample Matched Analysis
Authors: Ahmed A Kolkailah, Setri Fugar, Sagar Ranka, Jose Sleiman, Sameer A Hirji, Ahmed Al-Ogaili, Ali Ayoub, Luis H Paz Rios, Tania Campagnoli, Rami Doukky
Journal: Circulation (2018)

Background: Transcatheter aortic valve replacement (TAVR) is an established alternative treatment strategy to surgical aortic valve replacement (SAVR) in select patients with severe aortic stenosis (AS). Obstructive sleep apnea (OSA) is associated with increased perioperative morbidity and mortality. We sought to compare the in-hospital outcomes after SAVR and TAVR in patients with severe AS and OSA. Methods: We identified patients who underwent either SAVR or TAVR in the Nationwide Inpatient Sample (NIS) between 2012 and 2015 using ICD-9-CM procedure codes 35.21, 35.22 and 35.05, 35.06, respectively. We identified OSA with code 327.23. A 1:1 propensity-matched cohort was created to examine the primary endpoint of in-hospital mortality. Secondary endpoints included hospital length of stay (LOS), cost, and post-procedural complications. Results: We identified 1113 matched-pairs of TAVR and SAVR patients. The need for non-invasive ventilation was similar between TAVR and SAVR, respectively (9.3% vs. 10.4%, OR 0.88, p=0.36). However, TAVR patients had fewer respiratory complications, including pneumonia (0.5% vs. 1.3%, OR 0.43, p=0.08), acute respiratory failure (12.8% vs. 23.4%, OR 0.48), re-intubation (3.3% vs. 8.0%, OR 0.40), and tracheostomy (0.5% vs. 3.0%, OR 0.18), all p&lt;0.001. TAVR was also associated with significantly lower rates of acute myocardial infarction (1.9% vs. 4.7%, OR 0.39, p&lt;0.001), bleeding requiring blood transfusion (14.0% vs. 38.0%, OR 0.27, p&lt;0.001), and acute kidney injury (5.1% vs. 7.4%, OR 0.68, p&lt;0.03). However, TAVR did portend a greater risk of permanent pacemaker (PPM) implantation (24.7% vs. 6.8%, OR 4.55, p &lt;0.001). Although in-hospital mortality was similar between TAVR and SAVR (2.8% vs. 2.3%, OR 1.19, p=0.51), TAVR was associated with lower total median cost and shorter LOS ($206,585 vs. $222,805.50, p&lt;0.012 and 5 vs. 8 days, p&lt;0.001, respectively). Conclusions: In patients with severe AS and OSA, in-hospital mortality was comparable between TAVR and SAVR. Aside from higher risk of PPM implantation, TAVR was associated with significantly less post-operative complications, decreased total cost, and shorter LOS. These findings suggest that TAVR may be the preferred option in patients with severe AS and OSA.