tbuckley/cabot-search huggingface dataset:
Abstract 4540: Use of SIAH E3 ubiquitin ligase as a biomarker in pancreatic adenocarcinoma
Authors: Elizaevta Svyatova
Journal: Cancer Research (2016)

Abstract The dismal prognosis of patients diagnosed with pancreatic cancer points to our limited arsenal of effective anticancer therapies. Oncogenic K-RAS pathway activation is commonly detected in pancreatic cancer. These activations confer drug resistance, drive aggressive tumor growth and metastasis, and ultimately contribute to poor clinical outcome. Currently, there is no curative treatments for pancreatic cancers. Thus, early detection, biomarker discovery, and identifying novel means of countervailing hyperactive K-RAS signals are urgently needed. Seven-In-Absentia Homolog (SIAH), E3 ubiquitin ligase, is an essential downstream component of the RAS signal transduction pathway. SIAH is a member of a highly evolutionarily conserved family of RING finger E3 ubiquitin ligases. Our previous immunohistochemistry (IHC) studies have shown SIAH is a tumor-specific biomarker and SIAH expression is progressively increased as pancreatic tumor progresses from pancreatic intraepithelial neoplasia (PanIN) to pancreatic adenocarcinoma (PDCA) at late stages. In this study, we expand our observations by comparing the expression patterns of SIAH and several newly identified SIAH-interacting proteins using Mayo clinic pancreatic cancer SPORE tissue microarrays (TMA) in a hope of identifying new vulnerability and novel prognostic biomarkers in pancreatic cancer. We hypothesized that SIAH and SIAH-interacting proteins may serve as useful biomarkers and will help to assess effectiveness of anticancer treatment, disease progress, predict clinical outcome and patient survival in the clinical settings. Moreover, we are evaluating SIAH's role in the regulation of the SIAH-interacting proteins and validating the potential mechanisms of these dynamic interactions identified in vitro using pancreatic cancer patients TMA. Ultimately, we aim to explore the new cancer vulnerability, develop new therapeutic strategies, and validate novel prognostic biomarkers for pancreatic cancer patients. This study is performed in a double blind control settings and we are currently awaiting the disclosure of the clinical information from the pathologist. Citation Format: Elizaevta Svyatova. Use of SIAH E3 ubiquitin ligase as a biomarker in pancreatic adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4540.
Postremission Therapy in Adult Acute Myeloid Leukemia (AML): A Randomized Comparison between High Dose Ara-C Therapy and Conventional Consolidation Therapy (JALSG AML 201 Study).
Authors: Shuichi Miyawaki, Shigeki Ohtake, Shin Fujisawa, Hitoshi Kiyoi, Katsuji Shinagawa, Noriko Usui, Koichi Miyamura, Miki Nishimura, Yasushi Miyazaki, Kazuhiro Nishii, Tadashi Nagai, Takahisa Yamane, Masafumi Taniwaki, Masatomo Takahashi, Fumiharu Yagasaki, Yukihiko Kimura, Norio Asou, Sumihisa Honda, Kazunori Ohnishi, Tomoki Naoe, Ryuzo Ohno
Journal: Blood (2006)
Toxic Alcohol Calculations and Misinterpretation of Laboratory Results
Authors: Giuseppe Lippi, Mario Plebani
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
ABR, a Novel Inducer Of Transcription Factor C/EBPα, Is Necessary For Myeloid Differentiation and a Prognostic Factor In Acute Myeloid Leukemia
Authors: Carolina Yaeko Namasu, Dennis Gerloff, Alexander Arthur Wurm, Daniela Braeuer-Hartmann, Jens-Uwe Hartmann, Christiane Katzerke, Sebastian Schwind, Nadja Hilger, Stephan Fricke, Dietger Niederwieser, Gerhard Behre
Journal: Blood (2013)
The Diversification of Plant<i>NBS-LRR</i>Defense Genes Directs the Evolution of MicroRNAs That Target Them
Authors: Yu Zhang, Rui Xia, Hanhui Kuang, Blake C. Meyers
Journal: Molecular Biology and Evolution (2016)

High expression of plant nucleotide binding site leucine-rich repeat (NBS-LRR) defense genes is often lethal to plant cells, a phenotype perhaps associated with fitness costs. Plants implement several mechanisms to control the transcript level of NBS-LRR defense genes. As negative transcriptional regulators, diverse miRNAs target NBS-LRRs in eudicots and gymnosperms. To understand the evolutionary benefits of this miRNA-NBS-LRR regulatory system, we investigated the NBS-LRRs of 70 land plants, coupling this analysis with extensive small RNA data. A tight association between the diversity of NBS-LRRs and miRNAs was found. The miRNAs typically target highly duplicated NBS-LRRs. In comparison, families of heterogeneous NBS-LRRs were rarely targeted by miRNAs in Poaceae and Brassicaceae genomes. We observed that duplicated NBS-LRRs from different gene families periodically gave birth to new miRNAs. Most of these newly emerged miRNAs target the same conserved, encoded protein motif of NBS-LRRs, consistent with a model of convergent evolution for these miRNAs. By assessing the interactions between miRNAs and NBS-LRRs, we found nucleotide diversity in the wobble position of the codons in the target site drives the diversification of miRNAs. Taken together, we propose a co-evolutionary model of plant NBS-LRRs and miRNAs hypothesizing how plants balance the benefits and costs of NBS-LRR defense genes.
Noninvasive monitoring of dynamics of acquired EGFR-T790M mutation and discovery of its heterogeneity in patients with advanced NSCLC treated with EGFR-TKI.
Authors: Di Zheng, Xin Ye, Yun Sun, Meizhuo Zhang, Jiying Wang, Jie Zhang, Jian Ni, Ling Zhang, Haiping Zhang, Jie Luo, Liang Tang, Bo Su, Gang Chen, Guanshan Zhu, Yi Gu, Jianfang Xu
Journal: Journal of Clinical Oncology (2014)

11049 Background: EGFR-T790M mutation, a valuable target for next generation of EGFR-TKI, accounts for about half of acquired resistance to current EGFR-TKI therapy in EGFR sensitive mutation positive NSCLC patients. Noninvasive detection of EGFR-T790M in plasma circulating free DNA (cfDNA) has been proved to be feasible as re-biopsy of tumor tissue was challenging. However, clinical application of T790M plasma testing remains to be explored, particularly the rate and timing of detection, the status of co-existence with a sensitive mutation, and its potential impact on chemotherapy following EGFR-TKI resistance. Methods: A highly sensitive digital PCR method for EGFR mutation testing in plasma was developed and its high sensitivity and specificity were validated in testing cfDNA from EGFR-TKI-naïve NSCLC patients. This method was applied to detect T790M in plasma cfDNA from 66 post disease progression (PD) NSCLC patients, who developed acquired resistance to EGFR-TKI. Plasma samples before PD were available for some patients. Results: Overall, EGFR-T790M was detected in 36 out of 66 post-PD patients (54.5%). Among 10 of the 36 post-PD T790M+ patients, 5 (50%) were detected T790M+ during 1.5-3.5 months before PD. While T790M co-exists with a sensitive mutation in 30 of the 36 T790M+ patients (83.3%), T790M presents alone in 6 of the 36 patients (16.7%). Furthermore, dynamic quantitative changes of sensitive mutations and T790M in a few patients who received chemotherapy plus TKI after PD showed preliminary insight that, even in double mutant cases, T790M and sensitive mutant DNA might not always come from the same tumor cell populations, and the T790M heterogeneity status could affect outcome of chemotherapy following EGFR-TKI resistance. Conclusions: Noninvasive monitoring of plasma cfDNA could detect T790M with a positive rate similar to that reported in tumor tissue in advanced NSCLC patients treated with EGFR-TKI. T790M could be detected in plasma up to 3.5 months before clinical PD. T790M may present with or without EGFR sensitive mutation in tumor cells, and its heterogeneity status could affect outcome of chemotherapy following EGFR-TKI resistance.
P-218 Neo-adjuvant chemotherapy for patients with clinical T4 locally advanced colon cancer: short and long term outcomes
Authors: M. Verstegen, J.M. Gooyer, J. t'Lam-Boer, S. Radema, A. ten Tije, M. Elferink, C. Verhoef, A. Rijken, J.M.J. Schreinemakers, J. De Wilt
Journal: Annals of Oncology (2015)
A New Model to Predict Remission Status in Acute Myeloid Leukemia (AML) Patients Based on Day 14 Bone Marrow (D14 BM) Biopsy
Authors: Maxim Norkin, Myron Chang, An Qi, Helen Leather, Lakshmikanth Katragadda, Ying Li, Jan S Moreb, W. Stratford May, Randy A. Brown, Jack W. Hsu, John W Hiemenz, John R Wingard, Christopher R. Cogle
Journal: Blood (2015)
Abstract 1540: Midkine-raised oral cancer growth, migration and invasion is required for RBPJk modulation
Authors: Tai-Jan Chiu, Yi-Ching Chen, Chang-Han Chen
Journal: Cancer Research (2016)

Abstract Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck cancer, and its incidence has increased by 50% during the past decade. Despite the nowadays available therapeutic managements, such as surgery, radiotherapy, chemotherapy or in combination, the five-year survival rate is still improved. The current view is to present that the accumulations of genetic and epigenetic alterations in OSCC lead to the progression of cancer. Our previous study indicated that midkine, heparin-binding growth factor, was overexpressed in tumor tissues of head and neck cancer patients and its expression also correlated with poor 5-year survival. In this study, we tried to explore the biological functions and mechanisms of midkine in vitro and in vivo. Established gain-of-function of midkine in two oral cancer cell lines not only promoted cell growth by MTT, soft agar and BrdU assays, but also induced tumor growth in xenograft model. Midkine-overexpressing cells induced cell migration and invasion by wound healing and Transwell assays. Conversely, cell growth, migration and invasion were also inhibited; while endogenous midkine was abolished by midkine-mediated siRNA in oral cancer cells. By using bioinformatics, Q-RT-PCR, Western blotting, promoter assay and ChIP assay, we identified that RBP-Jk, a transcriptional factor, could bind to the promoter regions of midkine and to induce midkine expression in oral cancer cells. In the specimens of oral cancer patients, the expressions of midkine and RBP-Jk had a positive correlation by immunohistochemistry. Taken together, these results demonstrated that RBP-Jk regulates midkine expression and involves in midkine-elicited tumor formation in oral cancer. Citation Format: Tai-Jan Chiu, Yi-Ching Chen, Chang-Han Chen. Midkine-raised oral cancer growth, migration and invasion is required for RBPJk modulation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1540.
Effect of exercise training on C reactive protein: a systematic review and meta-analysis of randomised and non-randomised controlled trials
Authors: Michael V Fedewa, Elizabeth D Hathaway, Christie L Ward-Ritacco
Journal: British Journal of Sports Medicine (2016)

Purpose C-reactive protein (CRP) is a marker of chronic systemic inflammation frequently used in cardiovascular disease risk assessment. The purpose of this meta-analysis was to provide a quantitative estimate of the magnitude of change in CRP following participation in physical exercise interventions. Methods All studies included in the meta-analysis were peer reviewed and published in English. Human participants were assigned to a non-exercise comparison group or exercise training group, with the intervention lasting ≥2 weeks. CRP levels were measured at baseline, during and/or after completion of the exercise training programme. Random-effects models were used to aggregate a mean effect size (ES), 95% CIs and potential moderators. Results 83 randomised and non-randomised controlled trials met the inclusion criteria and resulted in 143 effects (n=3769). The mean ES of 0.26 (95% CI 0.18 to 0.34, p&lt;0.001) indicated a decrease in CRP following exercise training. A decrease in body mass index (BMI; β=1.20, SE=0.25, p&lt;0.0001) and %Fat (β=0.76, SE=0.21, p=0.0002) were associated with a decrease in CRP, independently accounting for 11.1% and 6.6% of the variation in response, respectively. Exercise training led to a greater reduction in CRP when accompanied by a decrease in BMI (ES=0.38, 95% CI 0.26 to 0.50); however, a significant improvement in CRP occurred in the absence of weight loss (ES=0.19, 95% CI 0.10 to 0.28; both p&lt;0.001). Conclusions These results suggest that engaging in exercise training is associated with a decrease in CRP levels regardless of the age or sex of the individual; however, greater improvements in CRP level occur with a decrease in BMI or %Fat.
High-Dose Rituximab In The Conditioning Regimen Before Allogeneic Stem Cell Transplantation Decreases Deaths Related To Gvhd Without Affecting The Anti-Lymphoma Effect
Authors: Anna Dodero, Francesco Spina, Barbara Sarina, Cristiana Carniti, Francesca Patriarca, Angelo Michele Carella, Alessandro Levis, Alberto Bosi, Michele Falda, Paolo Di Bartolomeo, Francesco Onida, Serena Dalto, Antonio Vendramin, Alessandro Rambaldi, Paolo Corradini
Journal: Blood (2013)
Pravastatin to prevent obstetrical complications in women with antiphospholipid syndrome
Authors: Maged M. Costantine
Journal: Journal of Clinical Investigation (2016)

Pregnant women with antiphospholipid syndrome (APS) are at a high risk of obstetrical complications. The current standard of care, including the use of low-dose aspirin and heparin, has not been shown to prevent preeclampsia or intrauterine growth restriction (IUGR). Due to the similarities in pathophysiology among preeclampsia, IUGR, and atherosclerotic cardiovascular disease, statins have been proposed for treating and/or preventing these obstetrical complications. In this issue of the JCI, Lefkou et al. report on a small, observational trial that showed a dramatic improvement in both maternal and fetal/neonatal outcomes in women with APS given pravastatin after the onset of preeclampsia and/or IUGR compared with women in the control group. These results, along with other recent clinical studies, support further evaluation of statins for prevention of preeclampsia in a large-scale randomized clinical trial.
Backlog and burden of fractures in Sierra Leone and Nepal: Results from nationwide cluster randomized, population-based surveys
Authors: Barclay T Stewart, Adam L Kushner, Thaim B Kamara, Sunil Shrestha, Shailvi Gupta, Reinou S Groen, Ben Nwomeh, Richard A Gosselin, David Spiegel
Journal: International Journal of Surgery (2016)
Abstract 1901: Leptin modulation of PCSC, HDAC, and microRNA in pancreatic adenocarcinoma
Authors: Cynthia M. Tchio, Adriana Harbuzariu, Tia Harmon, Derrick Beech, Ruben Gonzalez-Perez
Journal: Cancer Research (2016)

Abstract Background: Obesity is an important risk factor of Pancreatic Adenocarcinoma (PA) and it is characterized by the accumulation of excessive body fat and a Body Mass Index (BMI) value greater than 30. Obesity is also characterized by high levels of leptin, which has been consistently associated with the development of many different cancer including PA. Leptin can induce the proliferation of Pancreatic Cancer Stem Cells (PCSC), which are responsible for chemoresistance, invasiveness and reoccurrence of PA. PCSC express specific cell markers and can form tumorspheres in vitro. Obesity can alter the DNA acetylation and microRNA activity which are also linked to PA progression. We hypothesized that high level of leptin could modulate Histone Deacetylase (HDAC) and microRNA activity in PA cells, which induce PCSC changes and tumor progression. Methods: The PA cell lines were cultured in mammocult media that contained heparin and hydrocortisone, which will allow the proliferation of tumorspheres enriched with PCSCs. The cells were cultured with leptin, chemotherapeutic drug, and leptin signaling inhibitor IONP-LPrA2. Tumorspheres formation (number and size) was determined after 1 week of treatment. Additionally, the levels of PCSC markers, HDAC1, HDAC2, HDAC3, and HDAC8 in tumorspheres were determined using flow cytometry, western blot, and RT-PCR. In addition, the effects of treatments on miR21 and miR200a/c levels were determined using RT-PCR. Results: Leptin induced PA tumorspheres formation and size, which was accompanied by higher level of PCSC markers (CD24, CD44, ESA, and ALDH1). Moreover, leptin affected the level of HDACs, miR21 and miR200a/c in PA tumorspheres. IONP-LPrA2 abrogated leptin effects and decreased PCSC which were spared by chemotherapeutics. Conclusion: Obesity signals via leptin could be involved in the increase PA aggressiveness and chemoresistance, which may be linked to the increase of PCSC. Leptin could induce PA progression and chemoresistance via modulation of HDAC and miRNA. Acknowledgement: This work was supported by the DOD W81XWH-13-1-0382; NIH/SBIR1R41CA183399-01A1; Pilot Project Award from MSM/Tuskegee University/UAB Cancer Center Partnership grant 5U54CA118638; PC SPORE Grant from UAB to RRGP; Calvin Johnson Jr. Foundation Pancreatic Cancer Research Scholarship to CITM, and facility and support services at Morehouse School of Medicine (1G12RR026250-03; NIH RR03034 and 1C06 RR18386). Citation Format: Cynthia M. Tchio, Adriana Harbuzariu, Tia Harmon, Derrick Beech, Ruben Gonzalez-Perez. Leptin modulation of PCSC, HDAC, and microRNA in pancreatic adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1901.
CBM-14GLIOBLASTOMA CELLS EXPOSED TO 5-ALA RELEASE PROTOPORPHYRIN IX CONTAINING EXTRACELLULAR VESICLES DETECTABLE BY HIGH-RESOLUTION FLOW CYTOMETRY
Authors: Rosalie Schnoor, Sybren L.N. Maas, Ger J.A. Arkesteijn, Jeroen de Vrij, Pierre A. Robe, Marca H.M. Wauben, Esther N.M. Nolte - 't Hoen, Marike L.D. Broekman
Journal: Neuro-Oncology (2015)

INTRODUCTION: Gliolan or 5-aminolevulinic acid (5-ALA) is used for fluorescence-guided neurosurgery in glioblastoma multiforme (GBM) patients. 5-ALA is part of the heme synthesis pathway. In GBM cells, accumulation of fluorescent protoporphyrin IX (PpIX) is observed after oral intake, providing the neurosurgeon with visual guidance during surgery. Extracellular vesicles (EVs) or exosomes are nano-sized (50-1000 nm) lipid membrane-enclosed vesicles released by cells. We hypothesized that EVs from fluorescent GBM cells can contain PpIX and are thus fluorescent as well, allowing for tumor derived extracellular vesicle detection by high-resolution flow cytometry. METHODS: U87-MG/EGFRvIII cells were cultured for 24-hours in presence of 500uM 5-ALA. Extracellular vesicles were isolated from cell culture supernatant by sequential (ultra)centrifugation and analysed using high-resolution flow cytometry. Fluorescent EVs were spiked into platelet-free plasma from healthy donors at different concentrations. Subsequently, plasma samples from GBM patients treated with 5-ALA were studied using high-resolution flow-cytometry. RESULTS: GBM cells treated with 5-ALA released fluorescent extracellular vesicles, which could be detected by high-resolution flow cytometry (488 nm excitation). These fluorescent EVs could be reliably quantified when spiked into healthy donor platelet-free plasma. In platelet-free plasma from GBM patients treated with 5-ALA, fluorescent extracellular vesicles could be observed. CONCLUSION: Here we provide a novel method to identify tumor-derived extracellular vesicles using high-resolution flow cytometry of PpIX positive particles. Current research focuses on detection of these particles in GBM patient derived bodily fluids and their potential relation to tumor volume and response to therapy.
The Stepwise Increase in the Number of Transcription Factor Families in the Precambrian Predated the Diversification of Plants On Land
Authors: Bruno Catarino, Alexander J. Hetherington, David M. Emms, Steven Kelly, Liam Dolan
Journal: Molecular Biology and Evolution (2016)

The colonization of the land by streptophytes and their subsequent radiation is a major event in Earth history. We report a stepwise increase in the number of transcription factor (TF) families and subfamilies in Archaeplastida before the colonization of the land. The subsequent increase in TF number on land was through duplication within existing TF families and subfamilies. Almost all subfamilies of the Homeodomain (HD) and basic Helix-Loop-Helix (bHLH) had evolved before the radiation of extant land plant lineages from a common ancestor. We demonstrate that the evolution of these TF families independently followed similar trends in both plants and metazoans; almost all extant HD and bHLH subfamilies were present in the first land plants and in the last common ancestor of bilaterians. These findings reveal that the majority of innovation in plant and metazoan TF families occurred in the Precambrian before the Phanerozoic radiation of land plants and metazoans.