tbuckley/cabot-search huggingface dataset:
Gemcitabine resistance in cultured pancreatic tumor cells is associated with down regulation of PTEN and a mesenchymal phenotype
Authors: michael kim, Ami Shah, Jing Zhang, Nila Parikh, James Abbruzzese, Gary Gallick
Journal: Cancer Research (2008)

2460  The diagnosis of pancreatic cancer confers a grim prognosis that has changed little over the last 30 years. Although gemcitabine remains the cornerstone of chemotherapy in pancreatic cancer, its efficacy remains limited by the rapid development of tumor cell resistance which may involve redundant chemoresistance mechanisms and/or mesenchymal phenotypes. Utilizing two gemcitabine resistant pancreatic cancer cell lines previously isolated in our lab, the purpose of this study was to: 1) characterize the molecular mechanisms of gemcitabine resistance; 2) determine if common phenotypes and gene expression patterns could predict resistance; and 3) determine if gemcitabine resistance confers global resistance to other chemotherapeutic agents. For these studies, two gemcitabine-sensitive pancreatic cancer cell lines, ASPC-1 and L3.6pl, were maintained in increasing levels of gemcitabine until they developed stable resistance to supratherapeutic concentrations. Common phenotypic features were examined, including markers of epithelial-to-mesenchymal transition (EMT), stem cell marker expression, and sensitivity to oxaliplatin, dasatinib, and XL820 (c-Met inhibitor). As we reported previously, both resistant cell lines displayed hallmarks of EMT including fibroblast-like morphology, increased migration and invasion, increased vimentin, decreased E-cadherin expression, and increased nuclear expression of Twist. To validate these EMT findings, we examined EMT properties of naturally occurring sensitive and resistant lines, including Panc1, Miapaca2, BxPC3, MPANC96, CFPAC1, SU8686, HS766T, and HPDE. We demonstrated that in most cell lines, increased vimentin and decreased E cadherin (EMT characteristics) predicted resistance. We also sought to determine whether the more mesenchymal of our phenotypes conferred resistance to other chemotherapy agents. Both L3.6pl and L3.6plGR were equally sensitive to oxaliplatin. In addition, resistant L3.6pl cells demonstrated increased sensitivity to both dasatinib and XL820. As c-Met is activated in resistant cells, the latter finding suggests c-Met inhibition may sensitize cells to gemcitabine. Lastly, we examined PTEN, a gene product implicated in the self-renewal of cancer stem cells and, in turn, gemcitabine resistance. Relative to parental cells, both resistant lines exhibited decreased expression of PTEN and activation of the PI3K/Akt axis. These findings suggest a potential mechanism of gemcitabine resistance common to our phenotype. Thus, we conclude that PTEN expression and mediators of EMT may be important in the development and maintenance of gemcitabine phenotypes. Further, the sensitivity of the L3.6pl gemcitabine resistant phenotype to tyrosine kinase inhibitors may indicate reliance upon alternate survival elements in conjunction with the development of gemcitabine resistance.
The Exonization and Functionalization of an Alu-J Element in the Protein Coding Region of Glycoprotein Hormone Alpha Gene Represent a Novel Mechanism to the Evolution of Hemochorial Placentation in Primates
Authors: Haidi Chen, Li Chen, Yune Wu, Hao Shen, Guang Yang, Cheng Deng
Journal: Molecular Biology and Evolution (2017)

Alu elements contribute considerably to gene regulation and genome evolution in primates. The generation of new exons from Alu elements has been found in various human genes, and the regulatory function of the Alu exon has been investigated in many studies. However, the functionalization of Alu elements in protein coding regions remains unknown. Here, we reported that an Alu-J element exonized in the glycoprotein hormone alpha (GPHA) gene and encoded an additional N-terminal peptide (Alu-J encoding peptide) of the mature GPHA peptide, leading to a splicing variant of Alu-GPHA in anthropoid primates ∼35 Ma. Interestingly, adaptive evolution of the Alu-J exon occurred in the human and ape lineages during anthropoid evolution. The Alu-J encoding peptide is found to be a new biomarker in human early pregnancy and prolongs the serum half-life of human chorionic gonadotropin (HCG) circulation. Moreover, Alu-J encoding peptide enhances the bioactivity of HCG protein, both in vivo and in vitro. Our study reveals the first example of an Alu element functioning as the encoding peptide to increase the whole protein stability and provides insight into the potential multi-functionalization of the Alu exon in the protein coding regions. Furthermore, with the chorionic gonadotropin linking with hemochorial placentation, the exonization and functionalization of the Alu-J exon in GPHA gene represent a novel mechanism to the evolution of hemochorial placentation in primates.
Outcomes After Cryoablation Versus Partial Nephrectomy for Sporadic Renal Tumors in a Solitary Kidney: A Propensity Score Analysis
Authors: Bimal Bhindi, Ross J. Mason, Mustafa M. Haddad, Stephen A. Boorjian, Bradley C. Leibovich, Thomas D. Atwell, Adam J. Weisbrod, Grant D. Schmit, R. Houston Thompson
Journal: European Urology (2017)
The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology
Authors: Marc van Bilsen, Hitesh C. Patel, Johann Bauersachs, Michael Böhm, Martin Borggrefe, Dirk Brutsaert, Andrew J.S. Coats, Rudolf A. de Boer, Gilles W. de Keulenaer, Gerasimos S. Filippatos, John Floras, Guido Grassi, Ewa A. Jankowska, Lilian Kornet, Ida G. Lunde, Christoph Maack, Felix Mahfoud, Piero Pollesello, Piotr Ponikowski, Frank Ruschitzka, Hani N. Sabbah, Harold D. Schultz, Petar Seferovic, Riemer H.J.A. Slart, Peter Taggart, Carlo G. Tocchetti, Linda W. Van Laake, Faiez Zannad, Stephane Heymans, Alexander R. Lyon
Journal: European Journal of Heart Failure (2017)
9 Transforming transition for paediatric ibd patients in northern ireland
Authors: R Little, L McLoughlin, A Szabo
Journal: Gut (2017)

Background  The Paediatric Gastroenterology team in Belfast has been continuously developing their service to facilitate efficient transfer of adolescent care to Adult Gastroenterology. Initially this process was by referral letter only however, in view of the increasing prevalence of Inflammatory Bowel Disease (IBD), establishing a well-structured transition clinic was essential. We sought to elucidate the level of preparedness for, and experience at, transition clinic from our adolescent attendees.  Method  We devised a questionnaire which was distributed to all adolescent patients attending transition clinic over a six month period, which they completed anonymously. Data was then collated.  Results  Of the twenty two patients surveyed 100% rated the quality of care at transition clinic as excellent or good. 100% agreed they were well supported by the medical and nursing staff present, 82% of which agreed the clinic adequately prepared them for moving to Adult Gastroenterology care. However, only 50% of patients knew their medication names and doses. 32% wanted more advice regarding symptom management and investigations. 75% of patients had ongoing dietetic and psychology input. Concern regarding continuity of these valuable services and the loss of a supportive relationship with the paediatric nurse specialist were the main perceived stressors and anxieties for our patient cohort.  Conclusions  Over the last eight years the Paediatric Gastroenterology team has successfully established transition clinics with all five trusts across the province. Collaboration between the Paediatric and Adult Gastroenterology teams in Northern Ireland has transformed the continuity, safety and patient experience for young people with IBD transitioning between our expert services.
The Treatment of Actinic Keratoses—The Rule Rather Than the Exception
Authors: Bobbak Mansouri, Chad D. Housewright
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
End-of-Life Care in Older Patients After Serious or Severe Traumatic Brain Injury in Low-Mortality Hospitals Compared With All Other Hospitals
Authors: Elizabeth J. Lilley, John W. Scott, Joel S. Weissman, Anna Krasnova, Ali Salim, Adil H. Haider, Zara Cooper
Journal: JAMA Surgery (2017)

More than 80% of older patients die or are seriously impaired within 1 year after severe traumatic brain injury (TBI). Given their poor survival, information about end-of-life care is a relevant marker of high-value trauma care for these patients. In-hospital mortality is commonly used to measure quality of trauma care; however, it is not known what type of end-of-life care hospitals with the best survival outcomes provide to those who die.
Automated sub-cortical brain structure segmentation combining spatial and deep convolutional features
Authors: Kaisar Kushibar, Sergi Valverde, Sandra González-Villà, Jose Bernal, Mariano Cabezas, Arnau Oliver, Xavier Lladó
Journal: Medical Image Analysis (2018)

Sub-cortical brain structure segmentation in Magnetic Resonance Images (MRI) has attracted the interest of the research community for a long time as morphological changes in these structures are related to different neurodegenerative disorders. However, manual segmentation of these structures can be tedious and prone to variability, highlighting the need for robust automated segmentation methods. In this paper, we present a novel convolutional neural network based approach for accurate segmentation of the sub-cortical brain structures that combines both convolutional and prior spatial features for improving the segmentation accuracy. In order to increase the accuracy of the automated segmentation, we propose to train the network using a restricted sample selection to force the network to learn the most difficult parts of the structures. We evaluate the accuracy of the proposed method on the public MICCAI 2012 challenge and IBSR 18 datasets, comparing it with different traditional and deep learning state-of-the-art methods. On the MICCAI 2012 dataset, our method shows an excellent performance comparable to the best participant strategy on the challenge, while performing significantly better than state-of-the-art techniques such as FreeSurfer and FIRST. On the IBSR 18 dataset, our method also exhibits a significant increase in the performance with respect to not only FreeSurfer and FIRST, but also comparable or better results than other recent deep learning approaches. Moreover, our experiments show that both the addition of the spatial priors and the restricted sampling strategy have a significant effect on the accuracy of the proposed method. In order to encourage the reproducibility and the use of the proposed method, a public version of our approach is available to download for the neuroimaging community.
A phase I study of JS001, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with advanced solid tumors.
Authors: Zhihong Chi, Bixia Tang, Xinan Sheng, Lu Si, Chuanliang Cui, Yan Kong, Dan Li, Si Ming Li, Xieqiao Yan, Li Li Mao, Bin Lian, Xue Bai, Xuan Wang, Li Zhou, Jiayi Yu, Mingli Xu, Lihou Dong, Haifeng Song, Jun Guo
Journal: Journal of Clinical Oncology (2017)

3067 Background: JS001 blocks the interaction between PD-1 and its ligands and eradicates established tumor in human PD-1 Knock-in mouse model. Methods: A Phase I open-label study is designed to evaluate the safety and tolerability of JS001 in advanced solid tumor pts who are refractory to standard therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg followed by a dose expansion. (Clinical Trial ID: NCT02836795). Results: As of January 27, 2017, pts enrollment has been completed with 36 pts from 3 indications (22 Melanoma; 9 Urothelial Carcinoma; 5 Renal Cell Carcinoma). The majority of melanomas are acral and mucosal origin. No DLT was observed and no MTD was reached in the study. The most common treatment-related AEs were grade 1/2, including hyper- or hypo-thyroidism (42%), rash (39%), fever (28%), leukopenia (22%), elevation of liver enzymes (19%), anorexia (17%), and fatigue (14%). Treatment–related grade 3 AEs include proteinuria (n = 1), and lipase increase (n = 2). The emergence of AEs is not dose related. JS001 PK shows dose-dependent exposure with the elimination half-life of 6 to 12 days. Among 32 evaluable pts, 1 pt have complete response (melanoma), 6 pts have partial response (3 melanoma, 2 RCC and 1 UC), and 10 pts achieve stable disease, for an ORR of 22% and a DCR of 53%. 6 out of 7 CR/PR pts still have ongoing response. Two groups of pts benefited most from JS001 treatment, pts with high tumor-infiltrating lymphocytes (TIL) (50% ORR) and pts with &gt; 1% PD-L1 expression in tumor biopsy (46% ORR). Conclusions: JS001 exhibited a favorable safety profile in human. Treatment related AEs are in line with those from approved drugs in the same class. JS001 has demonstrated promising anti-tumor activity, especially in previously under-evaluated acral (20% ORR, 53% DCR) and mucosal (25% ORR, 50% DCR) melanomas. Clinical trial information: NCT02836795.
DESMAN: a new tool for de novo extraction of strains from metagenomes
Authors: Christopher Quince, Tom O. Delmont, Sébastien Raguideau, Johannes Alneberg, Aaron E. Darling, Gavin Collins, A. Murat Eren
Journal: Genome biology (2017)

We introduce DESMAN for De novo Extraction of Strains from Metagenomes. Large multi-sample metagenomes are being generated but strain variation results in fragmentary co-assemblies. Current algorithms can bin contigs into metagenome-assembled genomes but are unable to resolve strain-level variation. DESMAN identifies variants in core genes and uses co-occurrence across samples to link variants into haplotypes and abundance profiles. These are then searched for against non-core genes to determine the accessory genome of each strain. We validated DESMAN on a complex 50-species 210-genome 96-sample synthetic mock data set and then applied it to the Tara Oceans microbiome.
Phase III evaluation of American ginseng (panax quinquefolius) to improve cancer-related fatigue: NCCTG trial N07C2.
Authors: Debra L. Barton, Heshan Liu, Shaker R. Dakhil, Breanna M. Linquist, Jeff A. Sloan, Craig R. Nichols, Travis W. McGinn, Ernie P. Balcueva, Grant R. Seeger, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2012)

9001 Background: Ginseng is popularly used as a treatment for fatigue, one of the most common and disabling symptoms in people diagnosed with cancer. It is termed an “adaptogen”, thought to help the body combat negative effects of stress. This trial was to evaluate 2,000 mg American Ginseng versus placebo for cancer-related fatigue (CRF). Methods: Patients with cancer undergoing or having completed curative intent treatment and experiencing fatigue, rated at least 4 on a numeric analogue fatigue scale (1-10) for ≥1 month, were eligible. Exclusion criteria included CNS lymphoma, brain malignancies, or prior use of ginseng or chronic systemic steroids. Other etiologies for fatigue, such as pain and sleep, were also excluded. Patients were randomized to receive, in a double blind manner, 2,000 mg/d of American Ginseng or placebo in BID dosing for 8 weeks. The primary endpoint was change from baseline in the general subscale of the Multidimensional Fatigue Symptom Inventory (MFSI) at 4 weeks. Other MFSI subscales and the fatigue-inertia subscale of the Profile of Mood States (POMS) were also analyzed. Data were transformed to a 0-100 scale. Results: 364 patients were enrolled from 10/2008 to 07/2011. Data at 4 and 8 weeks are provided for several fatigue endpoints in the table below; higher numbers are better. Mental, emotional and vigor subscales of the MFSI were not significantly different between arms. There were no statistically significant differences in any grade of toxicity or self reported side effects between ginseng and placebo. Conclusions: This trial provides data to support that American Ginseng reduces general and physical CRF over 8 weeks without side effects. The treatment did not provide significant reductions in fatigue at 4 weeks and did not impact mental, emotional, and vigor dimensions of fatigue. [Table: see text]
H-1B Visa Applications for Physicians
Authors: Nkemakolam Iroegbu, Marko Jachtorowycz, Mike Sherman
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 16205: Oligogenic Inheritance in Dilated Cardiomyopathy is Illustrated in Non-segregating Lamin A/C (LMNA) Pedigrees
Authors: Jason R Cowan, Ana Morales, Daniel D Kinnamon, Michael J Bamshad, Deborah A Nickerson, Ray E Hershberger
Journal: Circulation (2016)

Introduction: We and others have proposed that, unlike many Mendelian diseases of monogenic cause, 20-30% of dilated cardiomyopathy (DCM) may be attributed to an oligogenic model wherein disease ri...
Change in circulating microRNA profile of obese children indicates future risk of adult diabetes
Authors: Xianwei Cui, Lianghui You, Lijun Zhu, Xing Wang, Yahui Zhou, Yun Li, Juan Wen, Yankai Xia, Xinru Wang, Chenbo Ji, Xirong Guo
Journal: Metabolism (2017)

Childhood obesity increases susceptibility to type 2 diabetes (T2D) in adults. Circulating microRNAs (miRNAs) in serum have been proposed as potential diagnostic biomarkers, and they may contribute to the progression toward T2D. Here, we investigated the possibility of predicting the future risk of adult T2D in obese children by using circulating miRNAs.We performed miRNA high-throughput sequencing to screen relevant circulating miRNAs in obese children. The expression patterns of targeted miRNAs were further explored in obese children and adults with T2D. To investigate the underlying contributions of these miRNAs to the development of T2D, we detected the impacts of the candidate miRNAs on preadipocyte proliferation, insulin secretion by pancreatic β-cell, and glucose uptake by skeletal muscle cells.Three miRNAs (miR-486, miR-146b and miR-15b), whose expression in the circulation was most dramatically augmented in obese children and adult T2D patients, were selected for further investigation. Of these 3 miRNAs, miR-486 was implicated in accelerating preadipocyte proliferation and myotube glucose intolerance, miR-146b and miR-15b were engaged in the suppression of high concentration glucose-induced pancreatic insulin secretion, and they all contributed to the pathological processes of obesity and T2D.Our results provide a better understanding of the role of circulating miRNAs, particularly miR-486, miR-146b and miR-15b, in predicting the future risk of T2D in obese children.
PAM50 Provides Prognostic Information When Applied to the Lymph Node Metastases of Advanced Breast Cancer Patients
Authors: Nicholas P. Tobin, Arian Lundberg, Linda S. Lindström, J. Chuck Harrell, Theodoros Foukakis, Lena Carlsson, Zakaria Einbeigi, Barbro K. Linderholm, Niklas Loman, Martin Malmberg, Mårten Fernö, Kamila Czene, Charles M. Perou, Jonas Bergh, Thomas Hatschek
Journal: Clinical Cancer Research (2017)

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting.Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan-Meier and/or multivariate Cox regression analyses.Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan-Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer-specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance.Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients. Clin Cancer Res; 23(23); 7225-31. ©2017 AACR.
Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer
Authors: R Tyler Hillman, Gary B Chisholm, Karen H Lu, P Andrew Futreal
Journal: JNCI Journal of the National Cancer Institute (2017)

To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes.