tbuckley/cabot-search huggingface dataset:
Carcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial-Mesenchymal Transition
Authors: Angela Pang, Mariana Carbini, Andre L. Moreira, Robert G. Maki
Journal: Journal of Clinical Oncology (2017)

In this review, we outline the biology and management of patients with carcinosarcomas and related malignancies, which are often included under the broader concept of sarcomatoid carcinomas. Carcinosarcomas are unusual tumors that are commonly gynecologic in origin, where they are referred to as malignant mixed Müllerian tumors, but may appear in any anatomic site. Although a variety of hypotheses have been presented as to the biphasic nature of these tumors, carcinosarcomas seem to represent the best example in human cancers of the concept of epithelial-mesenchymal transition (EMT), in which the two parts of the tumor are genomically related to one another, as opposed to the mesenchymal component that represents a second neoplasm or (benign) reactive process. In general, patients with carcinosarcomas fare worse than patients with carcinomas of the same anatomic site. Treatment paradigms for carcinosarcomas generally follow those of carcinomas of the same organ site, except where clinical trials provide more specific options. Agents that block or reverse EMT are worth examination in patients with carcinosarcoma and arguably may be even more effective in carcinomas, given evidence of dependence on EMT to generate successful metastases. Information about EMT may also inform other phase transitions in cancer, such as those between prostate or lung carcinoma and more aggressive tumors with neuroendocrine differentiation.
Wine glass size in England from 1700 to 2017: a measure of our time
Authors: Zorana Zupan, Alexandra Evans, Dominique-Laurent Couturier, Theresa M Marteau
Journal: BMJ (2017)

Wine, mistletoe's seasonal partner, 1 may be a feature of some rather merry Christmas nights, particularly for women. 2 As we approach the culturally legitimised deviancy of festive drinking, we suggest that size does matter: look at the wine glass in your hand.
Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA
Authors: Matthew A. Coelho, Sophie de Carné Trécesson, Sareena Rana, Davide Zecchin, Christopher Moore, Miriam Molina-Arcas, Philip East, Bradley Spencer-Dene, Emma Nye, Karin Barnouin, Ambrosius P. Snijders, Wi S. Lai, Perry J. Blackshear, Julian Downward
Journal: Immunity (2017)

The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the regulation of PD-L1 expression remains unclear. We report that oncogenic RAS signaling can upregulate tumor cell PD-L1 expression through a mechanism involving increases in PD-L1 mRNA stability via modulation of the AU-rich element-binding protein tristetraprolin (TTP). TTP negatively regulates PD-L1 expression through AU-rich elements in the 3′ UTR of PD-L1 mRNA. MEK signaling downstream of RAS leads to phosphorylation and inhibition of TTP by the kinase MK2. In human lung and colorectal tumors, RAS pathway activation is associated with elevated PD-L1 expression. In vivo, restoration of TTP expression enhances anti-tumor immunity dependent on degradation of PD-L1 mRNA. We demonstrate that RAS can drive cell-intrinsic PD-L1 expression, thus presenting therapeutic opportunities to reverse the innately immunoresistant phenotype of RAS mutant cancers.
Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes
Authors: Y-T Tang, D Wang, H Luo, M Xiao, H-S Zhou, D Liu, S-P Ling, N Wang, X-L Hu, Y Luo, X Mao, Q-L Ao, J Huang, W Zhang, L-S Sheng, L-J Zhu, Z Shang, L-L Gao, P-L Zhang, M Zhou, K-G Zhou, L-G Qiu, Q-F Liu, H-Y Zhang, J-Y Li, J Jin, L Fu, W-L Zhao, J-P Chen, X Du, G Huang, Q-F Wang, J-F Zhou, L Huang
Journal: Blood Cancer Journal (2017)

Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm sporadically affecting people from Asia and Central and South America.The median overall survival (OS) is less than 2 months, irrespective of treatments.Epstein-Barr virus (EBV) is mostly detected in the leukemia cells and is proposed to contribute to the pathogenesis of ANKL [1][2][3] .ANKL represents a distinct disease entity within the continuous spectrum of EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs).Patients with ANKL usually manifest a fulminant and extremely aggressive clinical course.However, some clinicopathologic features may be shared with different types of EBV-T/NK-LPDs, which leads to the occurrence of a few cases with features intermediate between two similar disorders 4-6 .The diagnosis of ANKL largely relies on the identification of morphologically and immunophenotypically aberrant leukemia cells 7 .Chromosomal gains and losses, activating STAT3 and STAT5 mutations, and HACE1 hypermethylation have only been sporadically detected [8][9][10] .Moreover, optimal therapy of ANKL has not yet been established 11 .To date, less than 350 cases of ANKL have been described in English literature worldwide.Because of the rarity of ANKL, the clinical features, potential pathogenesis, therapeutic strategies, and prognostic factors still lack in understanding.A multicenter
Myocardial Fibrosis in Competitive Triathletes Detected by Contrast-Enhanced CMR Correlates With Exercise-Induced Hypertension and Competition History
Authors: Enver Tahir, Jitka Starekova, Kai Muellerleile, Alexandra von Stritzky, Julia Münch, Maxim Avanesov, Julius M. Weinrich, Christian Stehning, Sebastian Bohnen, Ulf K. Radunski, Eric Freiwald, Stefan Blankenberg, Gerhard Adam, Axel Pressler, Monica Patten, Gunnar K. Lund
Journal: JACC. Cardiovascular imaging (2017)
The Effects of Sex-Biased Gene Expression and X-Linkage on Rates of Sequence Evolution in Drosophila
Authors: José Luis Campos, Keira J A Johnston, Brian Charlesworth
Journal: Molecular Biology and Evolution (2017)

A faster rate of adaptive evolution of X-linked genes compared with autosomal genes (the faster-X effect) can be caused by the fixation of recessive or partially recessive advantageous mutations. This effect should be largest for advantageous mutations that affect only male fitness, and least for mutations that affect only female fitness. We tested these predictions in Drosophila melanogaster by using coding and functionally significant noncoding sequences of genes with different levels of sex-biased expression. Consistent with theory, nonsynonymous substitutions in most male-biased and unbiased genes show faster adaptive evolution on the X. However, genes with very low recombination rates do not show such an effect, possibly as a consequence of Hill-Robertson interference. Contrary to expectation, there was a substantial faster-X effect for female-biased genes. After correcting for recombination rate differences, however, female-biased genes did not show a faster X-effect. Similar analyses of noncoding UTRs and long introns showed a faster-X effect for all groups of genes, other than introns of female-biased genes. Given the strong evidence that deleterious mutations are mostly recessive or partially recessive, we would expect a slower rate of evolution of X-linked genes for slightly deleterious mutations that become fixed by genetic drift. Surprisingly, we found little evidence for this after correcting for recombination rate, implying that weakly deleterious mutations are mostly close to being semidominant. This is consistent with evidence from polymorphism data, which we use to test how models of selection that assume semidominance with no sex-specific fitness effects may bias estimates of purifying selection.
Data-Driven Mammography Screening Practices—Reply
Authors: Cindy S. Lee, Edward A. Sickles, Elizabeth S. Burnside
Journal: JAMA Oncology (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 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
Biomacromolecules as carriers in drug delivery and tissue engineering
Authors: Yujie Zhang, Tao Sun, Chen Jiang
Journal: Acta Pharmaceutica Sinica B (2017)

Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.
Microprinted Stem Cell Niches Reveal Compounding Effect of Colony Size on Stromal Cells‐Mediated Neural Differentiation
Authors: Ramila Joshi, Pradip Shahi Thakuri, James C. Buchanan, Jun Li, Hossein Tavana
Journal: Advanced Healthcare Materials (2017)

Abstract Microenvironmental factors have a major impact on differentiation of embryonic stem cells (ESCs). Here, a novel phenomenon that size of ESC colonies has a significant regulatory role on stromal cells induced differentiation of ESCs to neural cells is reported. Using a robotic cell microprinting technology, defined densities of ESCs are confined within aqueous nanodrops over a layer of supporting stromal cells immersed in a second, immiscible aqueous phase to generate ESC colonies of defined sizes. Temporal protein and gene expression studies demonstrate that larger ESC colonies generate disproportionally more neural cells and longer neurite processes. Unlike previous studies that attribute neural differentiation of ESCs solely to interactions with stromal cells, it is found that increased intercellular signaling of ESCs significantly enhances neural differentiation. This study offers an approach to generate neural cells with improved efficiency for potential use in translational research.
Reprogramming of cellular metabolism: driver for airway remodelling in COPD?
Authors: Pieter S. Hiemstra, Anne M. van der Does
Journal: European Respiratory Journal (2017)

Mitochondrial dysfunction, in particular decreased oxidative phosphorylation and increased production of mitochondrial reactive oxidant species (ROS), and changes in cellular metabolism are increasingly recognised as important events in the pathogenesis of a range of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension and lung cancer [1, 2]. We are beginning to understand how dysfunction of the mitochondria is linked to the altered use of metabolic pathways and how this impacts cellular function. This switch in use of different metabolic pathways is often referred to as metabolic reprogramming, repatterning or rewiring. Mitochondrial dysfunction and metabolic reprogramming are important for understanding cancer, immunity and inflammation, but studies focused on tissue remodelling have also revealed a regulatory role of these mechanisms [1, 2]. Mitochondrial dysfunction and metabolic changes contribute to inflammation and tissue remodelling in COPD <http://ow.ly/hgsm30gARnv>
Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1‐PRKACA fusion
Authors: Rondell P. Graham, Carolin Lackner, Luigi Terracciano, Yessica González‐Cantú, Joseph J. Maleszewski, Patricia T. Greipp, Sanford M. Simon, Michael S. Torbenson
Journal: Hepatology (2017)

Fibrolamellar carcinomas are characterized by activation of protein kinase A, a kinase composed of catalytic and regulatory subunits. PRKACA encodes a catalytic subunit of protein kinase A, and almost all fibrolamellar carcinomas have a heterozygous 400‐kb deletion that leads to the fusion of DNAJB1 and PRKACA . The resulting DNAJB1‐PRKACA fusion transcript is believed to activate protein kinase A by dysregulation of the catalytic portion of the protein. In contrast, PRKAR1A encodes one of the regulatory subunits of protein kinase A. We hypothesized that loss of function of this regulatory unit could also lead to protein kinase A activation and thus to fibrolamellar carcinoma. Because PRKAR1A mutations underlie the Carney complex, we searched for liver tumors in individuals with the Carney complex. We identified 3 individuals with fibrolamellar carcinomas and a personal history of the Carney complex. All three tumors displayed the typical morphology of fibrolamellar carcinoma and were positive for arginase, cytokeratin 7, and cluster of differentiation 68. Fluorescence in situ hybridization was negative for PRKACA rearrangements. However, PRKAR1A sequencing identified pathogenic mutations in two of two cases with successful sequencing. In addition, all three cases were negative for PRKAR1A protein expression, consistent with inactivation of this key regulatory unit of protein kinase A. We also identified one additional fibrolamellar carcinoma in an individual without a documented history of the Carney complex who was negative for PRKACA rearrangements but had loss of PRKAR1A protein expression as well as PRKAR1A mutations. Conclusion : Fibrolamellar carcinoma can be part of the Carney complex; in this setting, fibrolamellar carcinomas have inactivating PRKAR1A mutations instead of the DNAJB1‐PRKACA fusion gene found in sporadic fibrolamellar carcinomas, providing an alternate means for activation of protein kinase A. (H epatology 2017).
Association of PDL1 expression with TP53, KRAS mutation, and microsatellite instability in Indonesian patients with colorectal cancer
Authors: T.P. Putra, G.D. Kusumo, A. Budiyati, F. Rexana, A. Sudoyo, A.N. Kurniawan, A.R. Utomo, A. Utama
Journal: Annals of Oncology (2017)
Early experience with IBM Watson for Oncology (WFO) cognitive computing system for lung and colorectal cancer treatment.
Authors: S.P. Somashekhar, Martín-J. Sepúlveda, Andrew D Norden, Amit Rauthan, Kumar Arun, Poonam Patil, Ramya Y Ethadka, Rohit C Kumar
Journal: Journal of Clinical Oncology (2017)

8527 Background: IBM Watson for Oncology is an artificial intelligence cognitive computing system that provides confidence-ranked, evidence-based treatment recommendations for cancer. In the present study, we examine the level of agreement for lung and colorectal cancer therapy between the multidisciplinary tumour board from Manipal Comprehensive Cancer Centre in Bangalore, India, and Watson for Oncology. Methods: Watson for Oncology is a Memorial Sloan Kettering Cancer Center (New York, USA) trained cognitive computing system that uses natural language processing and machine learning to provide treatment recommendations. It processes structured and unstructured data from medical literature, treatment guidelines, medical records, imaging, lab and pathology reports, and the expertise of Memorial Sloan Kettering experts to formulate therapeutic recommendations. Treatment recommendations are provided in three categories: recommended, for consideration and not recommended. In this report we provide the results of the independent and blinded evaluation by the multidisciplinary tumour board and Watson for Oncology of 362 total cancer cases comprised of 112 lung, 126 colon and 124 rectal cancers seen at the Centre within the last three years. The recommendations of the two agents were compared for agreement and considered concordant when the tumour board recommendation was included in the recommended or for consideration categories of the treatment advisor. Results: Overall, treatment recommendations were concordant in 96.4% of lung, 81.0% of colon and 92.7% of rectal cancer cases. By tumour stage, treatment recommendations were concordant in 88.9% of localized and 97.9% of metastatic lung cancer, 85.5% of localized and 76.6% of metastatic colon cancer, and 96.8% of localized and 80.6% of metastatic rectal cancer. Conclusions: Treatment recommendations made by the Manipal multidisciplinary tumour board and Watson for Oncology were highly concordant in the cancers examined. This cognitive computing technology holds much promise in helping oncologists make information intensive, evidence based treatment decisions.
Dilated Internal Thoracic Vertebral Venous Plexus Simulating Bone Metastases on FDG PET/CT
Authors: Nir Hod, Reut Anconina, Daniel Levin, Dina Ezroh Kazap, Sophie Lantsberg
Journal: Clinical Nuclear Medicine (2017)

A 42-year-old woman with a newly diagnosed malignant thymoma underwent FDG PET/CT, which demonstrated an increased uptake in anterior mediastinal tumor and several pleural masses in the right hemithorax, compatible with "drop metastases." In addition, contrast-enhanced CT images showed hyperdense abnormality in T2 vertebral body, congruent with intensely increased FDG uptake, raising suspicion of skeletal metastasis. This is a rare but important potential pitfall either in CT and FDG PET/CT-a "false-positive" bony lesion not attributed to skeletal metastasis but to dilated internal thoracic vertebral venous plexus associated with collateral circulation due to superior vena cava syndrome.
Predicting Relapse with Circulating Tumor DNA Analysis in Lung Cancer
Authors: Iñaki Comino-Mendez, Nicholas Turner
Journal: Cancer Discovery (2017)

Abstract Summary: Advances in circulating tumor DNA (ctDNA) analysis are revealing new treatment strategies for patients with cancer. Detection of residual disease with ctDNA analysis predicts relapse with high accuracy after treatment for early-stage lung cancer. Cancer Discov; 7(12); 1368–70. ©2017 AACR. See related article by Chaudhuri et al., p. 1394.
HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Sunil R. Hingorani, Lei Zheng, Andrea J. Bullock, Tara E. Seery, William P. Harris, Darren S. Sigal, Fadi Braiteh, Paul S. Ritch, Mark M. Zalupski, Nathan Bahary, Paul E. Oberstein, Andrea Wang-Gillam, Wilson Wu, Dimitrios Chondros, Ping Jiang, Sihem Khelifa, Jie Pu, Carrie Aldrich, Andrew E. Hendifar
Journal: Journal of Clinical Oncology (2017)

Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients and Methods Patients with previously untreated metastatic pancreatic ductal adenocarcinoma were randomly assigned to treatment with PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or nab-paclitaxel/gemcitabine (AG). Tumor HA levels were measured retrospectively using a novel affinity histochemistry assay. Primary end points were progression-free survival (PFS; overall) and thromboembolic (TE) event rate. Secondary end points included overall survival, PFS by HA level, and objective response rate. An early imbalance in TE events in the PAG arm led to a clinical hold; thereafter, patients with TE events were excluded and enoxaparin prophylaxis was initiated. Results A total of 279 patients were randomly assigned; 246 had HA data; 231 were evaluable for efficacy; 84 (34%) had HA-high tumors (ie, extracellular matrix HA staining ≥ 50% of tumor surface at any intensity). PFS was significantly improved with PAG treatment overall (hazard ratio [HR], 0.73; 95% CI, 0.53 to 1.00; P = .049) and for patients with HA-high tumors (HR, 0.51; 95% CI, 0.26 to 1.00; P = .048). In patients with HA-high tumors (PAG v AG), the objective response rate was 45% versus 31%, and median overall survival was 11.5 versus 8.5 months (HR, 0.96; 95% CI, 0.57 to 1.61). The most common treatment-related grade 3/4 adverse events with significant differences between arms (PAG v AG) included muscle spasms (13% v 1%), neutropenia (29% v 18%), and myalgia (5% v 0%). TE events were comparable after enoxaparin initiation (14% PAG v 10% AG). Conclusion This study met its primary end points of PFS and TE event rate. The largest improvement in PFS was observed in patients with HA-high tumors who received PAG. A similar TE event rate was observed between the treatment groups in stage 2 of the trial.
Response by Parkash et al to Letters Regarding Article, “Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control])”
Authors: Ratika Parkash, John L. Sapp, Jeff S. Healey, Anthony S.L. Tang
Journal: Circulation (2017)
Anti-inflammatory effects of adjunctive macrolide treatment in adults admitted to hospital with influenza: an open-label, randomised controlled trial
Authors: Nelson Lee, Chun-Kwok Wong, Martin C W Chan, Esther S L Yeung, Wilson W S Tam, Owen T Y Tsang, Kin-Wing Choi, Paul K S Chan, Angela Kwok, Grace C Y Lui, Wai-Shing Leung, Irene M H Yung, Rity Y K Wong, Catherine S K Cheung, David S C Hui
Journal: The Lancet (2017)