tbuckley/cabot-search huggingface dataset:
Engineering Multidimensional Evolutionary Forces to Combat Cancer
Authors: Caroline E. McCoach, Trever G. Bivona
Journal: Cancer Discovery (2019)

With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fitness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fitness relationships to improve outcomes of patients with cancer. SIGNIFICANCE: Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance.
The feasibility and tolerability of newer chemotherapy regimens in the adjuvant setting in older patients with breast cancer.
Authors: Rahul Ladwa, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2015)

e12019 Background: Breast cancer remains the commonest cause of cancer for females worldwide. One in four patients are diagnosed older than age 70. Relatively few patients over 65 years old are enrolled in adjuvant trials. The purpose of this analysis was to assess feasibility and tolerability of newer adjuvant chemotherapy in patients aged 65 or older. Methods: Data was retrospectively collected at a single Centre in Australia of patients who had undertaken adjuvant chemotherapy during 2009-2013 for breast cancer. Basic clinicopathological parameters, relative dose intensity (RDI) via the Hyrniuk method and complications of treatment were recorded. Results: Of the 67 patients identified, completion of planned chemotherapy was observed in 60% and a RDI ≥85% was maintained in 49%. Admissions were recorded in 54% whilst 25% had dose delays, 22% had febrile neutropenia and granulocyte- colony stimulating factor (G-CSF) was used in 78%. Common reasons for treatment discontinuation included peripheral neuropathy (23%) and febrile neutropenia (19%). A higher mean RDI was statistically associated with age < 70 years, absence of comorbidities, absence of admissions and the use of G-CSF. Conclusions: Completion of newer chemotherapy regimens is achievable whilst maintaining dose intensity. However tolerability of chemotherapy is suboptimal given the high rate of admissions and toxicity. Targeting supportive care measures such as primary G-CSF prophylaxis could enable better delivery of newer adjuvant chemotherapy whilst maintaining safety. N (%) Age 65-69 44 66 70-74 17 25 > 74 6 9 BMI BMI ≤ 25 21 31 BMI > 25 46 69 Number of comorbidities via CI 0 48 72 1+ 19 28 Tumour size < 2cm 27 40 2-5cm 33 49 > 5cm 7 10 Number of positive nodes 0 33 49 1-3 22 33 4+ 12 18 Hormone receptor status Positive 46 69 Negative 21 31 HER2 status Positive 18 27 Negative 49 73 Chemotherapy TC 14 21 FEC-D 23 34 AC-T 13 19 TCH 11 16 Other 6 9 Completion of planned chemotherapy Yes 40 60 No 27 40 Dose delays Yes 17 25 No 50 75 Dose intensity < 85% 34 51 85% or over 33 49 Number of admissions 0 31 46 1+ 36 54 Febrile neutropenia Yes 15 22 No 52 78 G-CSF Yes 52 78 No 15 22 Treatment discontinuation Febrile neutropenia 5 19 Peripheral neuropathy 6 23 Other toxicity 15 58
Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial
Authors: David A Palma, Robert Olson, Stephen Harrow, Stewart Gaede, Alexander V Louie, Cornelis Haasbeek, Liam Mulroy, Michael Lock, George B Rodrigues, Brian P Yaremko, Devin Schellenberg, Belal Ahmad, Gwendolyn Griffioen, Sashendra Senthi, Anand Swaminath, Neil Kopek, Mitchell Liu, Karen Moore, Suzanne Currie, Glenn S Bauman, Andrew Warner, Suresh Senan
Journal: The Lancet (2019)
The Deep Brain Stimulation “Twiddler Syndrome”
Authors: Eric Jackowiak, Parag G. Patil, Kelvin L. Chou
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology 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 Neurology journal
Risk factors for complications of Peripherally Catheters Central Insertion (PICC) of prolonged use in patients with solid tumors treated with chemotherapy.
Authors: David Morales Pancorbo, Jose Fuentes Pradera, Pedro Jimenez Vilches, Carmen Escassi, Desiree Macias Guerrero, Eva Fernandez Parra, Reyes Bernabe Caro, Amelia Lopez Ladron, Maria Rodriguez de la Borbolla, Adrian Sanchez, Inmaculada Gallego, Javier Salvador Bofill
Journal: Journal of Clinical Oncology (2015)

e20731 Background: PICC is offered to oncologic patients as a more comfortable and usefulness alternative for chemotherapy infusion. With the aim of analyze the rate of catheter-related events, potential risk factors for complications and the feasibility of using for long time we report the experience in our center. Methods: prospective study of patients with solid tumors and PICC inserted (Power PICC, single lumen 5 French, Bard Access Systems, Salt Lake City. UT) at Valme Hospital from January 1,2013 to December 31, 2014. The PICC were placed in the basilic vein ultrasound and RX guided by an expert physician.Patients were trained in catheter care by experienced staff.Clinical information and risk factors include: gender, stage, bevacizumab, antiagregant , erythropoiesis-stimulating agents and/or corticosteroid treatment, comorbidity, type of cancer, neutrophenic risk of chemotherapy, hospitalization, invasive procedure, time to PICC removement and event related to catheter. Results: We study 151 consecutive patients (mean age 57; range 23-85). The most common diagnoses were colorectal (CCR) (45%) and breast cancer (27.8%). 62.3% of them with advanced disease.PICCs were in place for 25667 catheter-days (median time 154 days; range 2 to 630 days). 29 PICCs (19,2%) were removed early because of any complication for a rate of 1.1 per 1000 catheter days.The rate of infection was 0, 27 per 1000 catheter days and the rate of thrombosis was 0,46 per 1000 catheter days.The mean duration of catheter was lower in < 65 years (p = 0,034; IC 95% -79,2 to -3,1) and longer in metastasis disease and CCR (p = 0,005 and p = 0,001).We found that infection events were more frequent in the first 3 months ( 71%, OR 8.75; p = 0,001; 95% CI 1.6 to 47.2). Patients with corticosteroid treatment had higher rate of infections (OR 5,7; p = 0,03; 95% CI 1.2 to 27) No differences have been seen in the other analyzed factors such as antiplatelet or bevacizumab treatment Conclusions: Prolonged use of PICC is safe in patients with cancer with a low incidence of complications. The use of corticosteroids is associated with a higher rate of infections, especially in the first three months of the PICC Insertion.
FRI-192-Tenofovir disoproxil fumarate treatment in chronic hepatitis B patients with cirrhosis reduces hepatic decompensation, hepatocellular carcinoma and death
Authors: Ken Liu, Jonggi Choi, An Le, Vincent Wai-Sun Wong, Stephen L. Chan, Mindie Nguyen, Young-Suk Lim, Grace Lai-Hung Wong
Journal: Journal of Hepatology (2019)
Long-lasting Consequences of Gun Violence and Mass Shootings
Authors: Ali Rowhani-Rahbar, Douglas F. Zatzick, Frederick P. Rivara
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
FRI-100-Protective effects of glutathione and lipoic acid against cadmium-induced oxidative stress in rat’s liver
Authors: Andrej Veljkovic, Gordana Kocic, Dusan Sokolovic, Branka Djordjevic, Tatjana Jevtovic, Jelena Basic, Milena Despotovic, Tatjana Cvetkovic, Ivana Stojanovic, Ruzica Nikolic, Jasmina Jovanovic, Dusica Pavlovic
Journal: Journal of Hepatology (2019)
Variations in Modeling for Treating Acute Stroke—Reply
Authors: Jessalyn K. Holodinsky, Michael D. Hill, Noreen Kamal
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology 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 Neurology journal
Abstract 16634: Bcl2 Associated Athanogene 3 Haplo-insufficiency Decreases Cardiac Function and Attenuates Response to Stress
Authors: Valerie D Myers, Jufang Wang, Jianliang Song, Xue-Qian Zhang, Jessica Kurth, Tijana Knezevic, Farzaneh G Tahrir, Manish K Gupta, Jennifer Gordon, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
Journal: Circulation (2017)

Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid protein found in the heart, skeletal muscle and many cancer cell types. In the heart, it inhibits apoptosis and enhances autophagy while facilitating excitation-contraction coupling. Patients with deletions or truncations of BAG3 have haplo-insufficency. We made a haplo-insufficient mouse model by flanking an allele of BAG3 with loxP recombination sites (BAG3fl/+). BAG3fl/+ crossed with α-MHC-Cre mice generated cardiac specific BAG3 haplo-insufficient mice (cBAG3+/-). We used echocardiography to assess the cardiac phenotype. At 12 weeks of age, cardiac myocytes were isolated and examined for contractile force, calcium transient [Ca]i amplitude and mitochondrial membrane potential. Compared with Cre-/-BAG3fl/+ littermates (control), heart size and left ventricular ejection fraction (LVEF) in cBAG3+/- mice were unchanged at 8 weeks of age despite a 50% decrease in cardiac BAG3 but by 12 weeks LVEF has declined in males but not in females (Fig 1A & B). ...
SAT-179-Human liver organoids culture as a novel in vitro model of HBV infection
Authors: Chuan Kok Lim, Bang M Tran, Byron Shue, Nicholas Eyre, Dustin Flanagan, Elizabeth Vincan, Danni Colledge, Stephen Locarnini, Erin McCartney, Edmund Tse, Andrew Ruszkiewicz, Michael Beard
Journal: Journal of Hepatology (2019)
Homoarginine Supplementation Improves Cardiac Function in a Murine Model of Ischaemic Heart Failure
Authors: D Atzler, D J McAndrew, M Crabtree, A Hale, J Bailey, K Cordts, J E Schneider, S Zervou, E Schwedhelm, S Neubauer, C A Lygate
Journal: Circulation (2015)
TCTAP A-060 Safety and Efficacy of Bioresorbable Scaffolds in Daily Practice: Experience from a Single Center in Taiwan
Authors: Tse-Husan Yang, En-Shao Liu, Guang-Yuan Mar, Chin-Chang Cheng, Cheng Chung Hung, Cheng-Hung Chiang, Feng Yu Kuo, Tung-Chen Yeh, Hsiang-Chiang Hsiao, Tao-Yu Lee, Hsin-Li Liang, Wei-Chun Huang, Chun-Peng Liu
Journal: Journal of the American College of Cardiology (2019)
ROCK Inhibition Induces Terminal Adipocyte Differentiation and Suppresses Tumorigenesis in Chemoresistant Osteosarcoma Cells
Authors: Nobuhiro Takahashi, Hiroyuki Nobusue, Takatsune Shimizu, Eiji Sugihara, Sayaka Yamaguchi-Iwai, Nobuyuki Onishi, Haruko Kunitomi, Tatsuo Kuroda, Hideyuki Saya
Journal: Cancer Research (2019)

Tumors comprise heterogeneous cell types including cancer stem cells (CSC), progenitor cells, and differentiated cells. Chemoresistance is a potential cause of relapse and a key characteristic of CSC, but the development of novel therapeutic approaches for targeting these cells has been limited. We previously established osteosarcoma-initiating (OSi) cells by introducing the gene for c-Myc into bone marrow stromal cells of Ink4a/Arf knockout mice. These OSi cells are composed of two distinct clones: highly tumorigenic cells (AX cells), similar to bipotent committed osteochondral progenitor cells, and tripotent cells of low tumorigenicity (AO cells), similar to mesenchymal stem cells. Here we show that depolymerization of the actin cytoskeleton induces terminal adipocyte differentiation and suppresses tumorigenesis in chemoresistant OSi cells. In contrast to AX cells, AO cells were highly resistant to conventional chemotherapeutic agents such as doxorubicin and were thus identified as chemoresistant cells. Inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) elicited terminal adipocyte differentiation in chemoresistant AO cells through negative regulation of the transcriptional coactivator megakaryoblastic leukemia 1 associated with actin depolymerization. The clinically administered ROCK inhibitor fasudil significantly suppressed growth in vitro and tumorigenicity in vivo of chemoresistant AO cells as well as of OSi cells. Our findings thus suggest a new therapeutic strategy based on the induction of trans-terminal differentiation via modulation of actin cytoskeleton dynamics for therapy-resistant osteosarcoma stem cells. SIGNIFICANCE: These findings suggest that induction of trans-terminal differentiation through regulation of actin dynamics is a potential novel therapeutic approach for targeting chemoresistant stem-like tumor cells.
SAT-404-Discordant NS5a but not NS3 RASs profile in liver and plasma compartments of HIV/HCV genotype 1a/4d infected patients
Authors: Riccardo Vercesi, Giulia Morsica, Hamid Hasson, Emanuela Messina, Adriano Lazzarin, Caterina Uberti-Foppa, Sabrina Bagaglio
Journal: Journal of Hepatology (2019)
FRI-271-Rifaximin alleviates endotoxemia with improved intestinal hyperpermeability with partially modified fecal microbiota in cirrhotic patients
Authors: Kosuke Kaji, Hiroaki Takaya, Soichiro Saikawa, Shinya Sato, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akanahe, Akira Mitoro, Hitoshi Yoshiji
Journal: Journal of Hepatology (2019)
At its best, peer review is wonderful to behold
Authors: M. Samimi, A. Anstey
Journal: British Journal of Dermatology (2017)

How do you feel when you receive an e‐mail from a top journal inviting you to peer review in your field of expertise? Is it optimistic enthusiasm for the opportunity to contribute to academic progress? Perhaps pride and joy at finally being recognized as an expert? Or maybe pride mixed with anxiety, as your head says 'no', but your heart says 'yes'? Alternatively, a sense of irritation that the journal is asking you again, so soon after your previous effort? Or maybe none of this, just an overwhelming and irrepressible tiredness, and a longing for a large glass of red wine? Peer reviewing is fundamental to academic publishing; editorial teams rely on their reviewers to identify important and novel research papers, and to reject papers that are flawed or lacking novelty. For papers that make the cut, peer reviewers also help authors to improve the quality of their submitted manuscripts. For reviewers, this work carries personal benefits, providing privileged access to the latest research, an opportunity to contribute to progress, and a tool for maintaining a critical mind and writing skills. In 2009, a large international survey conducted among 40 000 researchers reported that 90% believed that peer reviewing made them feel that they were 'playing an active role in their community'.1 Despite this benefit, finding good‐quality peer reviewers is not easy. Readers may be surprised to discover that even for a journal with a strong reputation, acceptance rates for peer review following initial e‐mail invitations are around 30–50%. In other words, an associate editor aiming for at least two peer reviewers for a paper would need to invite four or five experts. Not infrequently, some clearly talented reviewers may provide laconic reviews such as 'Well written. No changes needed. Accept', which is essentially no review at all. Thus, it is prudent for editors to aim to recruit three or four reviewers to ensure that at least two are of sufficient quality to be relied on when making a judgement on the paper. Overall, six or seven reviewers may need to be invited in order to ensure that at least two or three reliable reviews are received in a timely fashion. However, the number is usually less because the editorial team use tried and trusted reviewers who they know will provide high‐quality, swift reviews.
Development of a bispecific tetravalent CD33/CD3 TandAbfor the treatment of AML.
Authors: Uwe Reusch, Kristina Ellwanger, Michael Weichel, Vera Molkenthin, Judith A. Fox, Stefan Knackmuss, Ivica Fucek, Erich Rajkovic, Eugene Zhukovsky, Jeanmarie Guenot, Martin Treder
Journal: Journal of Clinical Oncology (2015)

7071 Background: Acute Myeloid Leukemia (AML) is a hematologic malignancy with dire prognosis; immunotherapy may offer a much needed alternative to cytotoxic chemotherapy. TandAbs are tetravalent, bispecific diabodies that exceed renal clearance limits, providing both avidity and pharmacokinetic advantages over monovalent bispecific constructs. To identify a potential immunotherapeutic for AML and other CD33+ hematologic malignancies, fully human T-cell recruiting, CD33-directed bispecific TandAbs were constructed and profiled for manufacturability, stability and pharmacologic activity. Methods: Anti-CD33 scFv with high affinity to both human and cynomolgus CD33 were selected from fully human scFv libraries using phage display. Stable anti-CD33 scFv were formatted into TandAbs; linker length and domain order/topology were also varied. Expression levels in stably transfected CHO cells, purification properties, and stability were evaluated. Mechanism-based functional assays measured CD33/CD3 TandAb-mediated cytotoxicity towards CD33+ target cells. T cell activation and proliferation in the presence and absence of target cells were also studied. In vitro safety assessments of specificity and cytokine release from T cells without target cells were performed. CD33/CD3 TandAbs were studied in prophylactic and established HL-60 xenograft models. Results: CD33/CD3 TandAbs with excellent production and stability profiles also had potent cytotoxic activity towards CD33+ target cells (EC50 < 10 pM). TandAbs demonstrated equivalent binding affinity and potency for human and cyno antigens, facilitating toxicity studies. T cell activation, proliferation and cytotoxicity were strictly linked to the presence of CD33+ target cells. CD33/CD3 TandAbs did not elicit cytokine release from T cells without target cells. Potent anti-tumor activity of CD33/CD3 TandAbs was observed in vivo. Conclusions: A human CD33/CD3 TandAb therapeutic candidate with a promising activity and safety profile to date warrants clinical development as a potential treatment for AML. Preclinical development is ongoing.
Abstract 16277: Gender-dimorphic Effect of Optic Atrophy Protein (OPA)-1 on Platelet Activation and Thrombosis
Authors: Rhonda A Souvenir, Trevor P Fidler, Andrew S Weyrich, E. Dale Abel
Journal: Circulation (2015)

Mitochondrial dysfunction is strongly associated with many disorders including metabolic and cardiovascular diseases and their complications. Preliminary studies of platelets from the Framingham offspring cohort, revealed enrichment in transcripts encoding for the mitochondrial dynamics proteins: optic atrophy-I in females, and mitofusin II in both genders that correlated with cardiovascular risk. These transcripts encode established regulators of mitochondrial fusion, electron transport complex (ETC) assembly and apoptosis, thereby suggesting that altered mitochondrial dynamics may contribute to platelet dysfunction. Thus, to determine whether the enrichment in OPA1 transcripts in females that correlates with increased CVD risk represents an adaptive or pathophysiological response, mice with platelet-specific deletion of OPA1 (pOPA-1 KO) were generated. Male pOPA-1 KO mice exhibited compromised cristae morphology and a 50% reduction in mitochondrial DNA. Additionally, mitochondrial function assessed by an extracellular flux analyzer (XF24 Seahorse biosciences) was reduced by 50%. Mitochondrial dysfunction in male pOPA-1 KO mice was associated with heightened agonist response (a hyperactive phenotype). Male pOPA-1 KO mice had a shortened time to stable occlusion of the carotid artery as assessed in vivo by rose Bengal photochemical injury, and were more prone to develop a thrombus (14/15 knockouts vs. 4/8 controls) following permanent ligation of the inferior vena cava. In contrast, cristae morphology was normal and mitochondrial DNA unchanged in females. Additionally, the females revealed no evidence of heightened agonist response or increased incidence of thrombus formation. Thus OPA1 plays an essential role in regulating platelet mitochondrial function, platelet activation and thrombosis in males but not in females. These findings suggest that whereas maintaining OPA1 expression might be a protective adaptation in males, OPA1 induction in platelets of females with diabetes might not protect against platelet hyperactivation.