tbuckley/cabot-search huggingface dataset:
Abstract 16965: Microvesicles Rescue Cardiomyocytes From Doxorubicin Injury in a Patient Specific Model of Anthracycline Induced Cardiomyopathy
Authors: Connor G O’Brien, Liye Shi, Michelle R Santoso, Ji-Hye Jung, Evgeniya Vaskova, Gentaro Ikeda, Mehmet O Ozen, Utkan Demirci, Phillip C Yang
Journal: Circulation (2018)

Introduction: Anthracyclines are highly effective chemotherapeutic agents associated with cardiac toxicity. Anthracycline induced cardiomyopathy (AIC) carries a reported mortality rate in excess of 20% at four years on medical therapy. Effective therapies for AIC have not been established. The Stem Cell Injection for Cancer Survivors (SeNeCA) trial is examining the role of allogenic mesenchymal stem cell (MSC) therapy in treating AIC. To understand the mechanism and predict the efficacy of MSCs in myocardial recovery, we evaluated the restorative effects of MSCs following doxorubicin (dox) administration in vitro , employing iPSC- derived cardiomyocytes (iCM) generated from trial patients. Hypothesis: MSCs will rescue AIC patient-specific iCM from dox injury. Methods and Results: We generated three AIC patient-specific iPSC lines from SeNeCA patients. In vitro dox sensitivity was shown to be comparable to published values for AIC patient iCM. iCM were then cultured in 1μM dox for 24hrs and assessed for viability and apoptosis 72- hours post-injury by annexin-PI, ApoLive Glo, and tetrazolium (MTT) assay. MSC efficacy was assessed using co-culture. 2.5 x 10^5 iCM were plated and co-cultured with 2.5 x 10^5 MSC using a 1μm pore trans-well system. Compared to monoculture, MSC co-culture improved post- doxorubicin iCM viability significantly (50.0±4.0%* vs 35.7±0.8%, *p-value&lt; 0.005) by MTT and reduced apoptosis significantly (40.4±2.9%* vs 48.6±0.8%, *p-value&lt;0.01). Reactive oxygen species (ROS) production was also reduced (25.5%* vs 16%) by CellRox. MSC-derived microvesicles (MV) were assessed as potential effector molecules. MV demonstrated a dose- dependent effect with statistically significant improvement in viability achieved at a dose of ~500 MV/cell (44.5±4.4%* vs. 34.9±4.4%, *p-value&lt;0.06) by MTT. Results were corroborated by ApoLive Glo and annexin PI showing significantly reduced apoptosis and increased viability. Conclusion: Allogeneic MSCs can attenuate apoptosis and ROS production following doxorubicin injury in patient-specific iCM. This effect is largely mediated via MV. Our findings will be validated by the SeNeCA trial demonstrating proof-of-concept in in vitro clinical trials employing iPSC-derivatives.
Abstract P5-05-09: Chemo-sensitization of triple negative breast cancer by targeting RNA-binding protein HuR
Authors: Xiaoqing Wu, Lanjing Wei, Gulhumay Gardashova, Cuncong Zhong, Lan Lan, Qi Zhang, Dan A Dixon, Danny R Welch, Jeffrey Aubé, Liang Xu
Journal: Cancer Research (2020)

Abstract Triple negative breast cancer (TNBC) has a lower 5-year survival rate and higher recurrence rate compared to other types of breast cancer, which is partially due to the acquired resistance to current treatment regimens. The RNA-binding protein Hu antigen R (HuR) is overexpressed in breast cancer. Cytoplasmic HuR accumulation correlates with high-grade malignancy, poor distant disease-free survival and serves as a prognostic factor for poor clinical outcome in breast cancer. HuR promotes tumorigenesis by promoting mRNA stability and translation of proteins implicated in proliferation, survival, angiogenesis, invasion, and metastasis. HuR also modulates sensitivity of breast cancer cells to chemotherapy. HuR knockout in TNBC cells with high HuR sensitizes them to chemotherapy while HuR overexpression induces chemo-resistance. Meanwhile, chemotherapy promotes cytoplasmic HuR accumulation and increases expression of HuR target encoding proteins in TNBC cells. Therefore, there is a positive feedback loop between HuR and chemo-resistance. These findings suggest that HuR plays a critical role in promoting a drug-resistance mechanism and HuR is a potential target for developing a novel therapy to overcome chemo-resistance in TNBC. RNA-binding proteins such as HuR had previously been considered to be “undruggable” due to the lack of a well-defined binding pocket for target RNAs. Nevertheless, using high throughput screening followed by structure-based rational design and lead optimization, we have identified small molecules that potently inhibit HuR-mRNA interaction with nM to sub-µM potency. Our top HuR inhibitor, KH-3, inhibits TNBC cell growth in vitro and in vivo. KH-3 also sensitizes TNBC cells to docetaxel and doxorubicin treatment in vitro. Furthermore, acquired docetaxel-resistant MDA-MB-231 cells and doxorubicin-resistant MDA-MB-231 cells display similar sensitivity to KH-3 to their parental cells. In the study of mechanism of action, several HuR direct targets are found to be involved in acquired docetaxel and doxorubicin resistance. KH-3 can disrupt the interaction of HuR with those target mRNAs. In animal efficacy studies, the combination of KH-3 and chemotherapy shows synergistic effect in both parental and acquired resistant cell xenograft models. Our data provide a proof-of-principle that HuR inhibition by KH-3 may be developed as a promising molecular therapy to overcome chemo-resistance of TNBC with high HuR. Citation Format: Xiaoqing Wu, Lanjing Wei, Gulhumay Gardashova, Cuncong Zhong, Lan Lan, Qi Zhang, Dan A Dixon, Danny R Welch, Jeffrey Aubé, Liang Xu. Chemo-sensitization of triple negative breast cancer by targeting RNA-binding protein HuR [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-09.
Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization
Authors: Frank Yeung, Ying-Han Chen, Jian-Da Lin, Jacqueline M. Leung, Caroline McCauley, Joseph C. Devlin, Christina Hansen, Alex Cronkite, Zac Stephens, Charlotte Drake-Dunn, Yi Fulmer, Bo Shopsin, Kelly V. Ruggles, June L. Round, P’ng Loke, Andrea L. Graham, Ken Cadwell
Journal: Cell Host & Microbe (2020)
Abstract P1-13-02: Dynamic changes in high-sensitivity cardiac troponin I in response to anthracycline-based chemotherapy-The Cardiac Care Trial pilot data
Authors: Olga Oikonomidou, Evangelos Tzolos, Philip D Adamson, Peter S Hall, Iain R MacPherson, Morag MacLean, Steff Lewis, Heather McVicars, David E Newby, Nicholas L Mills, Ninian Lang, Peter A Henriksen
Journal: Cancer Research (2020)

Abstract BACKGROUND Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. PATIENTS AND METHODS This was a multi-centre prospective observational cohort study. Female patients with newly-diagnosed invasive breast cancer scheduled to receive adjuvant or neo-adjuvant anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was performed before, during and 24 hours after each treatment cycle. Plasma hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay (limit of detection 1.2 ng/L, coefficient of variation ≤10% at 4.7 ng/L, 99th centile upper reference limit in women 16 ng/L). RESULTS We recruited 78 women with a mean (standard deviation) age of 53.6 (9.6). The median (IQR) baseline troponin concentration was 1 (1 to 4) ng/L and median (IQR) cumulative epirubicin dose was 394 (300 to 405) mg/m2. Following an initial 33% fall 24 hours following anthracycline dosing (p &amp;lt;0.001), hs-cTnI concentrations increased by a median of 50% (p&amp;lt;0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately prior to the sixth treatment cycle of whom 21 (46.6%) had hs-cTnI concentrations ≥16 ng/L indicating myocardial injury. Plasma hs-cTnI concentrations prior to the second treatment cycle were a strong predictor of subsequent myocardial injury. CONCLUSIONS Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. More than one third of patients will develop biochemical evidence of chronic myocardial injury with plasma hs-cTnI concentrations above the 99th centile upper reference limit. This injury is most reliably determined from blood sampling performed before rather than during or after each treatment cycle. Citation Format: Olga Oikonomidou, Evangelos Tzolos, Philip D Adamson, Peter S Hall, Iain R MacPherson, Morag MacLean, Steff Lewis, Heather McVicars, David E Newby, Nicholas L Mills, Ninian Lang, Peter A Henriksen. Dynamic changes in high-sensitivity cardiac troponin I in response to anthracycline-based chemotherapy-The Cardiac Care Trial pilot data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-13-02.
Two Cobalt Chelatase Subunits Can Be Generated from a Single chlD Gene via Programed Frameshifting
Authors: Ivan V Antonov
Journal: Molecular Biology and Evolution (2020)

Magnesium chelatase chlIDH and cobalt chelatase cobNST enzymes are required for biosynthesis of (bacterio)chlorophyll and cobalamin (vitamin B12), respectively. Each enzyme consists of large, medium, and small subunits. Structural and primary sequence similarities indicate common evolutionary origin of the corresponding subunits. It has been reported earlier that some of vitamin B12 synthesizing organisms utilized unusual cobalt chelatase enzyme consisting of a large cobalt chelatase subunit (cobN) along with a medium (chlD) and a small (chlI) subunits of magnesium chelatase. In attempt to understand the nature of this phenomenon, we analyzed >1,200 diverse genomes of cobalamin and/or chlorophyll producing prokaryotes. We found that, surprisingly, genomes of many cobalamin producers contained cobN and chlD genes only; a small subunit gene was absent. Further on, we have discovered a diverse group of chlD genes with functional programed ribosomal frameshifting signals. Given a high similarity between the small subunit and the N-terminal part of the medium subunit, we proposed that programed translational frameshifting may allow chlD mRNA to produce both subunits. Indeed, in genomes where genes for small subunits were absent, we observed statistically significant enrichment of programed frameshifting signals in chlD genes. Interestingly, the details of the frameshifting mechanisms producing small and medium subunits from a single chlD gene could be prokaryotic taxa specific. All over, this programed frameshifting phenomenon was observed to be highly conserved and present in both bacteria and archaea.
Successful ongoing retreatment with glecaprevir/pibrentasvir + sofosbuvir + ribavirin in a patient with HCV genotype 3 who failed glecaprevir/pibrentasvir with both NS3 and NS5A resistance
Authors: M. Aragri, M. Milana, V.C. Di Maio, I. Lenci, L. Carioti, C.F. Perno, V. Svicher, M. Angelico, F. Ceccherini-Silberstein
Journal: Clinical Microbiology and Infection (2020)
Abstract P3-08-51: Association between BRCA mutational status and survival in patients with breast cancer: A meta-analysis
Authors: Miao Liu, Shu Wang
Journal: Cancer Research (2020)

Abstract Background: BRCA mutated breast cancer is associated with an aggressive phenotype with marked differences in histological grade and distant metastases and sensitive to PARPi and platinum therapy. Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results due to the differences in clinical and pathological status among study population. Therefore, we assessed the impact of BRCA mutations on survival of BC patients, based on their baseline characteristics and follow-up durations. Methods: Using PICO framework, articles comparing survival outcomes of BC patients having BRCA mutations against sporadic BRCA phenotype were retrieved from PubMed, EMBASE and Cochrane Library. Overall survival (OS) was the primary outcome, with disease free survival (DFS), distant metastasis free survival (DMFS) and breast cancer specific survival (BCCS) as the secondary outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Sub-group analysis was performed for survival based on age, tumor stage, estrogen receptor status, triple negative breast cancer (TNBC) status, tumor stage (Stage I-III vs I-IV) and follow-up durations. Results: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included in the analysis. In BRCA1/2+ group, no significant difference in OS and DFS than BRCA- group were observed (HR: 0.98, 1.36, respectively),have a better DMFS in BRCA- patients than that in BRCA1/2+ patients (HR: 1.32; 95% CI: 0.71, 2.44). However, the difference observed between the groups was insignificant (P = 0.3825). BRCA1+ patients had significantly lower OS (HR [95%CI]: 1.2 [1.08, 1.33]; P&amp;lt;0.001),poor BCSS at 10 years follow-up. DMFS was significantly poor in BRCA1+ patients compared with BRCA- patients both at 5 years follow-up (HR [95%CI]: 1.07 [1.04, 1.10]; P&amp;lt;0.0001) and 10 years follow-up (HR [95%CI]: 1.21 [1.13, 1.29]; P&amp;lt;0.0001).BRCA2+ patients had significantly lower DFS (HR [95%CI]: 1.35 [1.1, 1.67]; P = 0.0049) and BCSS (HR [95%CI]: 1.46 [1.26, 1.7]; P&amp;lt;0.0001) than BRCA2- patients. Among TNBC patients, OS was non-significantly better in BRCA1/2+ patients (HR 0.96, P = 0.803) than in BRCA- patients. However, DFS was significantly poor in BRCA1+ TNBC patients than BRCA1-/TNBC patients (HR [95% CI]:1.65 [1.08, 2.54]; P = 0.0216).Conclusion: BRCA1/2 mutation is associated with poor prognosis in patient with breast cancer. Hence, BRCA testing might help assess patient prognosis and treatment such as PARPi and platinum. Citation Format: Miao Liu, Shu Wang. Association between BRCA mutational status and survival in patients with breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-51.
Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease
Authors: John A. Spertus, Philip G. Jones, David J. Maron, Daniel B. Mark, Sean M. O’Brien, Jerome L. Fleg, Harmony R. Reynolds, Gregg W. Stone, Mandeep S. Sidhu, Bernard R. Chaitman, Glenn M. Chertow, Judith S. Hochman, Sripal Bangalore
Journal: New England Journal of Medicine (2020)

In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status.
Double Counting of Patients in Meta-analyses of Observational Studies
Authors: Warren Fingrut, Luke Y. C. Chen
Journal: JAMA Oncology (2020)

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
Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome
Authors: Jacob Schreiber, Timothy Durham, Jeffrey Bilmes, William Stafford Noble
Journal: Genome biology (2020)

The human epigenome has been experimentally characterized by thousands of measurements for every basepair in the human genome. We propose a deep neural network tensor factorization method, Avocado, that compresses this epigenomic data into a dense, information-rich representation. We use this learned representation to impute epigenomic data more accurately than previous methods, and we show that machine learning models that exploit this representation outperform those trained directly on epigenomic data on a variety of genomics tasks. These tasks include predicting gene expression, promoter-enhancer interactions, replication timing, and an element of 3D chromatin architecture.
Low Expression of T/NK-Cell Signature Predicts Poor Survival in Patients with Primary Testicular and Diffuse Large B-Cell Lymphoma
Authors: Suvi-Katri Leivonen, Marjukka Pollari, Oscar Bruck, Teijo Pellinen, Marja-Liisa Karjalainen-Lindsberg, Susanna Mannisto, Pirkko-Liisa Kellokumpu-Lehtinen, Satu Mustjoki, Sirpa Leppa
Journal: Blood (2017)
Response to letter titled ‘Reduction of HbA1c in patients with type 2 diabetes following duodenal mucosal resurfacing: could other factors be at play?’
Authors: JJGHM Bergman
Journal: Gut (2020)

We agree with Johnston and colleagues1that it is important to consider potential confounding factors, such as diet and exercise, when interpreting the results of our study.2 

Our study did not include specific dietary counselling of patients, and there was no concerted effort to have patients adhere to a specific hypocaloric regimen. During follow-up visits, patients underwent per protocol (PP) dietary counselling based on standard clinical practice guidelines. These guidelines emphasise the relation of carbohydrate intake, glycaemic index and blood glucose control. Taking into account that patients willing to participate in a study are generally more motivated to make behavioural changes, it is possible that the subjects in …
Abstract P1-05-06: Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers
Authors: Daeseok Kim
Journal: Cancer Research (2020)

Abstract Genomic analyses have revealed that many RNA species other than protein-coding mRNAs are transcribed from mammalian genomes and may have profound effects on cellular physiology and pathology. One such class of RNAs are the long noncoding RNAs (lncRNAs). In our previous work using Global Run-On and sequencing (GRO-seq), we identified and annotated ~1,900 lncRNAs in MCF-7 human breast cancer cells, which are differentially expressed across the distinct molecular subtypes of breast cancer. Further meta-analysis identified lncRNA152 as a predictor of increased metastasis-free survival. Thus, lncRNA152 levels may serve as a biomarker to track disease progression in breast cancer patients. However, the precise mechanisms by which lncRNA152 regulates these clinical outcomes remain largely unknown. Interestingly, lncRNA152 is highly expressed in the luminal subtypes of breast cancer, but downregulated in triple-negative breast cancers (TNBC), suggesting that lncRNA152 expression may be associated with more aggressive cancer features. Through multiple complementary experimental approaches, we found that (1) FoxA1 regulates lncRNA152 transcription, (2) knockdown of lncRNA152 inhibits the growth, but promotes cell migration and invasion, of luminal breast cancer cell subtypes, and (3) ectopic overexpression of lncRNA152 inhibits TNBC cell growth, migration, and invasion. Importantly, our xenograft studies provide evidence that lncRNA152 inhibits estrogen-dependent tumor growth of luminal and TNBC cells. In addition, transcriptome analysis of TNBC cell-derived xenografts indicates that lncRNA152 expression downregulates many genes that are involved in biological processes such as cell growth, migration, invasion, and angiogenesis. Collectively, these results suggest that lncRNA152 is a novel tumor suppressor in luminal and basal subtype of breast cancer. This work is supported by grants from the Cancer Prevention and Research Institute of Texas (CPRIT RP160318/RP190235) to W.L.K. Citation Format: Daeseok Kim. Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-06.
Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study
Authors: Ying-Jun Chang, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, None Wei-Han, Yu-Qian Sun, Chen-Hua Yan, Fei-Fei Tang, Xiao-Dong Mo, Yan-Rong Liu, Kai-Yan Liu, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation. Methods We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT ( n = 169) or MSDT ( n = 39). Results The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19–33%) and 44% (95% CI, 28–60%) for HIDT and MSDT, respectively ( P = 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31–63% vs. 23%, 95% CI, 17–29%; P = 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27–59% vs. 65%, 95% CI, 58–72%; P = 0.023) and overall survival (OS; 46%, 95% CI, 30–62% vs. 68%, 95% CI, 61–75%; P = 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1–19% vs. 11%, 95% CI, 6–16%; P = 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202–0.655; P = 0.001) and better LFS (HR = 0.414; 95% CI, 0.246–0.695; P = 0.001) and OS (HR = 0.380; 95% CI, 0.220–0.656; P = 0.001). Conclusions HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population. Trial registration ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014. https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&amp;draw=2&amp;rank=1 .
Underwater endoscopic mucosal resection for complete R0 removal of an adenoma extending deep into a colonic diverticulum
Authors: Kazuo Shiotsuki, Kenichiro Imai, Kinichi Hotta, Sayo Ito, Yoshihiro Kishida, Hiroyuki Ono
Journal: Endoscopy (2020)

Endoscopic removal of a colorectal polyp involving a diverticulum is challenging owing to the risk of perforation from lack of the muscularis propria [1] and concerns over incomplete resection associated with the difficult access [2].