tbuckley/cabot-search huggingface dataset:
Unmet Needs in Clinical Research in Breast Cancer: Where Do We Need to Go?
Authors: Ann H. Partridge, Lisa A. Carey
Journal: Clinical Cancer Research (2017)

Abstract This CCR Focus highlights areas in breast cancer research with the greatest potential for clinical and therapeutic application. The articles in this CCR Focus address the state of the science in a broad range of areas with a focus on “hot” although sometimes controversial topics, unanswered questions, and unmet need. From mutational signatures, the cancer genomic revolution, and new inroads in immunotherapy for breast cancer to unique concerns of vulnerable populations as well as national and global health disparities, these works represent much of the promise of breast cancer research as well as the challenges in the coming years. Each review focuses not only on recent discoveries but also on putting the topic in context, including limitations to overcome. This overview is designed to further contextualize the highlighted issues within the broader research landscape. We also present new information from a poll of ALLIANCE for Clinical Trials in Oncology Breast Committee members regarding the most needed and viable potential future National Cancer Institute (NCI)–supported clinical trials in breast cancer. The great challenge is to translate the potential benefits of greater scientific knowledge reflected in this CCR Focus section into improvements in outcomes for individuals and populations with breast cancer. A unifying theme across the six articles contained in this CCR Focus is the increasingly recognized value and necessity of collaboration across disciplines from bench to bedside to populations. Only continued and iteratively amplified scientific, clinical, and governmental commitment to creating, testing, and implementing new knowledge will reduce the global morbidity and mortality of breast cancer. Clin Cancer Res; 23(11); 2611–6. ©2017 AACR. See all articles in this CCR Focus section, “Breast Cancer Research: From Base Pairs to Populations.”
Myeloperoxidase/HLA Class II Complexes Recognized by Autoantibodies in Microscopic Polyangiitis
Authors: Ryosuke Hiwa, Koichiro Ohmura, Noriko Arase, Hui Jin, Kouyuki Hirayasu, Masako Kohyama, Tadahiro Suenaga, Fumiji Saito, Chikashi Terao, Tatsuya Atsumi, Hirotsugu Iwatani, Tsuneyo Mimori, Hisashi Arase
Journal: Arthritis & Rheumatology (2017)

Objective Autoantibodies against myeloperoxidase (MPO) that are expressed in neutrophils play an important role in the pathogenesis of microscopic polyangiitis (MPA). We recently observed that misfolded cellular proteins are transported to the cell surface by HLA class II molecules and are targeted by autoantibodies in patients with rheumatoid arthritis or antiphospholipid syndrome, suggesting that HLA class II molecules play an important role in autoantibody recognition. The aim of this study was to address the role of HLA class II molecules in the cell surface expression of MPO in patients with MPA. Methods The association of MPO with HLA–DR was analyzed using MPO and HLA–DR transfectants as well as neutrophils from healthy donors and patients with MPA. Autoantibody binding to the MPO/HLA–DR complex was analyzed by flow cytometry. The association of MPO with HLA–DR was assessed using the immunoprecipitation technique. The function of MPO–antineutrophil cytoplasmic antibody (ANCA) was assessed using a neutrophil‐like cell line expressing HLA–DR and MPO. Results MPO protein was detected on the cell surface in the presence of HLA–DR, and the MPO/HLA–DR complex was recognized by MPO‐ANCA. A competitive inhibition assay suggested that MPO associated with HLA–DR expresses cryptic autoantibody epitopes for MPO‐ANCA. Autoantibody binding to the MPO/HLA–DR complex was correlated with disease susceptibility conferred by each HLA–DR allele, suggesting that the MPO/HLA–DR complex is involved in the pathogenicity of MPA. Indeed, MPO–HLA class II complexes were detected in neutrophils from a patient with MPA as well as in cytokine‐stimulated neutrophils from healthy donors. Moreover, MPO‐ANCA stimulated MPO/HLA–DR complex–expressing HL‐60 cells. Conclusion Our findings suggest that MPO complexed with HLA class II molecules is involved in the pathogenesis of MPA as a target for MPO‐ANCA.
Investigational tests and treatments performed in terminal-stage cancer patients in two weeks before death: Supportive care study group in Turkish Oncology Association.
Authors: Ibrahim Turker, Seref Komurcu, Ali Arican, Filiz Cay Senler, Ozgur Ozyilkan, Hasan Senol Coskun, Dilsen Colak, Emel Ucgul, Alper Ata, Ahmet Sezer, Havva Yesil Cinkir, Fikret Arpaci
Journal: Journal of Clinical Oncology (2014)

e20503 Background: Although more palliative care is necessary for terminally ill cancer patients, excess investigational tests, invasive procedures and treatment is given instead. Methods: Between November 2009 and December 2013, six hundred and twenty-four patients with end stage cancer who were died at hospital evaluated retrospectively. Patients’ characteristics, sites of tumor and metastasis, tests and invasive procedures, treatments performed in the last two weeks before death were collected by chart review analysis. Results: Median age of 624 patients were 58 (range16-96) years. More than half of the patients (370, 54.7%) were men. The most frequent cancer sites were gastrointestinal (GI) system (32.2%), lung (24.0%), and breast (11.1%). Frequent metastatic sites were liver (34.8%), bone (31.5%), lung (23.3%) and/or brain (16.9%). Causes of death were respiratory failure, infections, and/or liver failure in 49.9%, 23.9% and 19.4% of patients, respectively. Radiological tests performed in the last two weeks before death were ultrasonography, computed tomography, magnetic resonance imaging, bone scan in 25.6%, 16.3%, 11.4%, and 3.8% of patients respectively. Treatments received were intravenous (i.v) serum infusion, blood transfusion, total parenteral nutrition(TPN), human albumin infusion in 55.9%, 44.1%, 34.9%, and 9.5% of patients respectively. Invasive procedures such as invasive pain relief, terminal sedation and chemotherapy performed in 12.6%, 4.4%, and 8.2% of patients respectively. Central venous catheter application, paracentesis, thoracentesis, GI endoscopy were applied in 41.7%, 9.8%, 5.6% and 3.4% of the patients, respectively. Conclusions: Radiological tests, invasive procedures, TPN and human albumin transfusion were used excessively in terminal stage cancer patients in our medical oncology inpatient clinics. Invasive pain relief, terminal sedation were still underused in our cancer clinics. There is an urgent need in developing national palliative care program to improve the understanding of end of life care in our medical oncology clinics.
Dose Escalation Optimization in Patients With Locally Advanced Non–Small-Cell Lung Cancer
Authors: Jing Zeng, Ramesh Rengan
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
Acute Pancreatitis Has a Long-term Deleterious Effect on Physical Health Related Quality of Life
Authors: Jorge D. Machicado, Amir Gougol, Kimberly Stello, Gong Tang, Yongseok Park, Adam Slivka, David C. Whitcomb, Dhiraj Yadav, Georgios I. Papachristou
Journal: Clinical Gastroenterology and Hepatology (2017)
A phase II study of temsirolimus in previously treated advanced hepatocellular carcinoma (HCC).
Authors: Jasgit C. Sachdev, Ahmed Y Javed, Alva Bowen Weir, Ronald I Korn, Shannon M Gulla, Ronald G Newbold, Matthew Smeltzer, Raymond U Osarogiagbon
Journal: Journal of Clinical Oncology (2014)

4098 Background: After Sorafenib failure,there is no effective systemic therapy for advanced HCC. Preclinical data show upregulated mTOR signaling in HCC. We tested the IV mTOR inhibitor (i), Temsirolimus (T), as salvage therapy for HCC. Methods: Patients (Pts) had locally advanced or metastatic HCC, progressed on or intolerant of sorafenib, Child Pugh A/B liver cirrhosis, ECOG 0-2. Primary end point of this Simon 2-stage, single-arm phase II study was 3 month PFS. ≥ 1/15 Pts in stage 1 and ≥ 4/25 Pts overall had to achieve this endpoint to reject the H0 (Type I and II errors 0.05 and 0.1). We gave 25 mg T weekly until progression or intolerance, with CT/MRI scans Q 6 wks. Modified (m) RECIST for HCC was used. Results: See the Table for Pt characteristics. 17 Pts progressed or died (4 still on study, 4 off study without progression). 13/23 (57%; 95% CI: 34-77%) evaluable Pts were alive without progression at 3 months. Median PFS, 17 wks (95% CI 12-35 wks); PFS at 24 wks, 37%; median OS, 30 wks (95% CI: 27-44 wks). Of 21 Pts evaluable by mRECIST, best responses were 8 PR (38%), 10 SD (48%) and 3 PD (14%) for a disease control rate at ≥ 12 weeks of 43% (9/21). Mean and median decreases in target lesions from baseline were 33% and 23% respectively. Exploratory textural analysis of baseline scans correlated with response (p = 0.008) suggesting a predictive CT marker for anti-tumor activity. Grade 3/4 treatment related AE in ≥10% Pts: thrombocytopenia, neutropenia, AST elevation and hyperglycemia. 2 on-treatment deaths occurred, both unrelated to drug. Conclusions: T showed higher responses than previously reported with systemic Rx for HCC. The primary end point was met with >1/2 of the Pts progression free at 3 months, and >1/3 at 6 months. We speculate that IV administration may have overcome compliance issues in drug administration, favorably impacting efficacy, as reflected by the response rates in this study, in contrast with those reported with the oral mTORi. Confirmatory studies with novel correlative biomarkers should clarify the role of this mTORi in HCC. Clinical trial information: NCT01567930. Enrolled 26 Evaluable 25 Median age (range) 62 (52-89) Male 23 Female 2 AA 13 Caucasian 12 Child Pugh A B 17 8 BCLC stage A B C D 1 2 22 0 Hepatitis B Y N 1 24 Hepatitis C Y N 16 9 Prior Rx Resection RFA TACE Sorafenib Chemotherapy 4 4 16 25 2
What's in a name?
Authors: P McCrory
Journal: British Journal of Sports Medicine (2001)

Warm upA whiV of the future I was intrigued to read in the press recently, a story based on a new study published by de Boer in the journal, Geology, that in Ancient Greece, the oracle at Delphi was probably in a state of a drug induced trance when advising supplicants.Plutarch, the historian, who was also the high priest at the temple of Apollo in Delphi, describes how the high priestess who spoke the oracles inhaled "sweet smelling vapours" in her chasm under the temple.De Boer and his coworkers discovered that the walls of this chasm or adytum contain volatile gases from the bituminous limestone that lies beneath the temple.The most common of these gases was ethylene, which smells sweet and moreover breathing it often induces a state of euphoria.Sometimes people have a more violent reaction.They become delirious and thrash around-a state that Plutarch also recorded.The high priestess, it seems, was as much a glue sniVer as a guru.It is interesting how attitudes change.What was seen in Ancient Greece as prophecy would today be seen as a social problem.Glue sniYng and other illicit drug use are banes of urban society.In sport, drug use is widespread.Both recreational drugs as well as performance enhancing or ergogenic agents are a commonplace feature of elite competition.We are no longer shocked when athletes are sent home from competition, stripped of their records or medals or stopped www.bjsportmed.com
The effect of 100% oxygen on tidal breathing parameters in preschool children
Authors: Rachel E. Foong, Alana J. Harper, Graham L. Hall, Kathryn A. Ramsey
Journal: European Respiratory Journal (2017)

The multiple-breath nitrogen washout (MBN2W) test assesses ventilation distribution by determining the number of functional residual capacity (FRC) lung turnovers required for tidal breathing of 100% oxygen to wash out resident nitrogen from the lungs [1]. In particular, the test has gained significant interest as a tool for monitoring disease progression and prognosis in children with lung disease, with a specific focus on cystic fibrosis (CF) due to its ability to discriminate between health and disease [2]. The use of 100% oxygen has become the preferred choice of inert gas in older children and adults. However, as discussed in the European Respiratory Society/American Thoracic Society consensus statement, there are disadvantages and unknowns as to how patient age, sedation and sleep state may interact with 100% oxygen to alter breathing patterns [3]. It is known that 100% oxygen alters breathing patterns in infants [4, 5] and therefore this approach is not recommended in this age group; however, it is assumed that the effect of 100% oxygen on respiration is diminished beyond infancy [3], with no reported impact of 100% oxygen on breathing parameters in school-aged children [6]. It remains unknown whether hyperoxia affects tidal breathing in young children, as there are no published studies in this age range. This study aimed to determine whether breathing 100% oxygen altered tidal breathing parameters in healthy young children and young children with CF. Multiple breath nitrogen washout does not cause physiologically relevant breathing changes in preschool children <http://ow.ly/xv9B30a0c7L> We would like to acknowledge Caroline Gallagher and Jasmine Grdosic (both from the Telethon Kids Institute, Perth, Australia) for assistance with patient recruitment and study measurements.
Glycemic Control and Functionality in Nursing Homes—More Than HbA<sub>1c</sub>—Reply
Authors: Sei J. Lee
Journal: JAMA Internal Medicine (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 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
In Reply
Authors: Antonio Santillan, Robert E. Bristow
Journal: Journal of Clinical Oncology (2006)

answer to that question is no. 8 In patients who reached only partial response after six cycles, does radiotherapy reverse the odds?No randomized study is available, and the results have been yes in the EORTC experience 8 and no in the German and French experiences. 5,6 Regarding chemotherapy, we remark that the LY09 study concurs to the demonstration, made since 1975, that ABVD provides results superior to those of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and its avatars. 9 We agree that, in the Hasenclever model, freedom from progression would better be correlated to actual, rather than to intended doses.In the LY09 trial, as approximately all drugs were administered at greater than 80% of intended dose (Table 3), the correlation between actual or intended dosing is probably close and could be checked.Finally, Johnson et al produced extremely valuable data, particularly on individual drug doses, with thorough analyzes.These data will contribute to designing improved trials where chemotherapy and radiation will be balanced according to the respective parts they take to cure Hodgkin's lymphoma in each different setting.
A Phase 1B Study of CC-122 in Combination with Obinutuzumab (GA101) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Indolent Non-Hodgkin Lymphoma
Authors: Jean-Marie Michot, Jeanette K Doorduijn, Reda Bouabdallah, Umberto Vitolo, Pier Luigi Zinzani, Marie Jose Kersten, Annalisa Chiappella, Rafael Sarmiento, Marlene Zuraek, Michael Pourdehnad, Kristen Hege, Zariana Nikolova, Vincent Ribrag
Journal: Blood (2016)
Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-β and Cardiac Fibrosis
Authors: Panagiotis Flevaris, Sadiya S. Khan, Mesut Eren, Adam J. T. Schuldt, Sanjiv J. Shah, Daniel C. Lee, Sweta Gupta, Amy D. Shapiro, Paul W. Burridge, Asish K. Ghosh, Douglas E. Vaughan
Journal: Circulation (2017)

Fibrosis is the pathological consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels of plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency of PAI-1 is associated with spontaneous age-dependent, cardiac-selective fibrosis in mice. We have identified a novel PAI-1-dependent mechanism that regulates cardiomyocyte-derived fibrogenic signals and cardiac transcriptional pathways during injury.Cardiac fibrosis in subjects with homozygous mutation in SERPINE-1 was evaluated with late gadolinium-enhanced cardiac magnetic resonance imaging. A murine cardiac injury model was performed by subcutaneous infusion of either saline or Angiotensin II by osmotic minipumps. We evaluated blood pressure, cardiac function (by echocardiography), fibrosis (with Masson Trichrome staining), and apoptosis (with TUNEL staining), and we performed transcriptome analysis (with RNA sequencing). We further evaluated fibrotic signaling in isolated murine primary ventricular myocytes.Cardiac fibrosis was detected in 2 otherwise healthy humans with complete PAI-1 deficiency because of a homozygous frameshift mutation in SERPINE-1. In addition to its suppressive role during spontaneous cardiac fibrosis in multiple species, we hypothesized that PAI-1 also regulates fibrosis during cardiac injury. Treatment of young PAI-1-/- mice with Angiotensin II induced extensive hypertrophy and fibrotic cardiomyopathy, with increased cardiac apoptosis and both reactive and replacement fibrosis. Although Angiotensin II-induced hypertension was blunted in PAI-1-/- mice, cardiac hypertrophy was accelerated. Furthermore, ventricular myocytes were found to be an important source of cardiac transforming growth factor-β (TGF-β) and PAI-1 regulated TGF-β synthesis by cardiomyocytes in vitro as well as in vivo during cardiac injury. Transcriptome analysis of ventricular RNA after Angiotensin II treatment confirmed that PAI-1 deficiency significantly enhanced multiple TGF-β signaling elements and transcriptional targets, including genes for extracellular matrix components, mediators of extracellular matrix remodeling, matricellular proteins, and cardiac integrins compared with wild-type mice.PAI-1 is an essential repressor of cardiac fibrosis in mammals. We define a novel cardiomyocyte-specific regulatory mechanism for TGF-β production by PAI-1, which explains the paradoxical effect of PAI-1 deficiency in promoting cardiac-selective fibrosis. Thus, PAI-1 is a molecular switch that controls the cardiac TGF-β axis and its early transcriptional effects that lead to myocardial fibrosis.
Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment
Authors: Rakiba Belkhir, Sébastien Le Burel, Laetitia Dunogeant, Aurélien Marabelle, Antoine Hollebecque, Benjamin Besse, Alexandra Leary, Anne-Laure Voisin, Clémence Pontoizeau, Laetitia Coutte, Edouard Pertuiset, Gaël Mouterde, Olivier Fain, Olivier Lambotte, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. <h3>Methods</h3> This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR. <h3>Results</h3> In 10 patients who received ICI therapy (all anti-PD-1 or anti-PDL1 antibodies), RA or PMR developed at a median of 1 month (1 to 9) after exposure. No patient had pre-existing rheumatic or autoimmune disease. RA developed in six patients; all six were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and four for rheumatoid factor. Anti-CCP antibodies were detected in two out of three patients tested before immunotherapy. Disease-modifying antirheumatic drugs were needed for three patients; the three others received corticosteroids or non-steroid anti-inflammatory drugs. PMR was diagnosed in four patients, all responded to corticosteroids. Despite these IrAEs, immunotherapy was pursued for all but one patient until cancer progression. <h3>Conclusions</h3> This is the first description of RA occurring after ICI therapy for cancer. PMR can also occur after ICI, particularly after anti-PD-1 therapy. All cases responded to corticosteroids or with immunosuppressive therapy. Collaboration between rheumatologists and oncologists is crucial and could lead to better recognition and care of these patients.
68Ga-PSMA PET/MR–Positive Peritoneal Metastasis in the Falciform Ligament in Recurrent Prostate Cancer
Authors: Benedikt Kranzbühler, Sébastien Tran, Thomas Zilli, Irene A. Burger
Journal: Clinical Nuclear Medicine (2017)

Synchronous or metachronous metastases develop in approximately one third of all prostate cancer (PCa) patients. Main sites of metastasis include lymph nodes, bone, lung and liver. Secondary peritoneal carcinomatosis is very rare in PCa, with only a few published cases. Ga-PSMA PET-based imaging is a promising tool for staging and restaging PCa. We report a case of Ga-PSMA PET/MR-positive peritoneal metastasis as site of primary relapse after definitive PCa treatment in a 58-year-old man with a prostate-specific antigen of 30 ng/mL at time of the study. Exploratory laparoscopy and subsequent histopathologic examination confirmed nonascitic peritoneal PCa carcinomatosis.