tbuckley/cabot-search huggingface dataset:
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
Authors: Mansoor R. Mirza, Bradley J. Monk, Jørn Herrstedt, Amit M. Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A. Ledermann, Domenica Lorusso, Ignace Vergote, Noa E. Ben-Baruch, Christian Marth, Radosław Mądry, René D. Christensen, Jonathan S. Berek, Anne Dørum, Anna V. Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J. Rimel, Joseph Buscema, John P. Balser, Shefali Agarwal, Ursula A. Matulonis
Journal: New England Journal of Medicine (2016)

Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
O-026 Combination of encorafenib and cetuximab with or without alpelisib in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC): phase 2 results
Authors: J. Tabernero, R. van Geel, T. Guren, R. Yaeger, A. Spreafico, J. Faris, T. Yoshino, Y. Yamada, W. Kim Tae, J. Bendell, M. Schuler, H.-J. Lenz, F. Eskens, J. Desai, H. Hochster, E. Avsar, T. Demuth, V. Sandor, E. Elez, J. Schellens
Journal: Annals of Oncology (2016)
Deterioration of pulmonary hypertension and pleural effusion with bosutinib following dasatinib lung toxicity
Authors: Marianne Riou, Andrei Seferian, Laurent Savale, Marie-Camille Chaumais, Christophe Guignabert, Matthieu Canuet, Pascal Magro, Delphine Rea, Olivier Sitbon, Xavier Jaïs, Marc Humbert, David Montani
Journal: European Respiratory Journal (2016)

Tyrosine kinase inhibitors (TKIs) targeting BCR/ABL such as imatinib, nilotinib, dasatinib, bosutinib and ponatinib have revolutionised the management of patients with chronic myeloid leukaemia (CML) [1]. Pleural effusions and pulmonary arterial hypertension (PAH) have been reported in patients treated with these agents [2–4]. These side-effects are more frequently observed with dasatinib use, with partial or complete reversibility after drug withdrawal [3]. Bosutinib is a second-generation TKI prescribed in case of intolerance or resistance to imatinib, nilotinib or dasatinib. In the present report, we describe two cases of worsening of dasatinib-induced PAH and two cases of severe pleural effusions, suggesting overlapping pulmonary toxicity of bosutinib and dasatinib. Pulmonary complications of bosutinib therapy and potential cross-intolerance with dasatinib <http://ow.ly/UKWu303KGhx> We acknowledge the French pulmonary hypertension pharmacovigilance network, VIGIAPATH, supported by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM).
Phase Ib study of CNTO 888 (anti-CCL 2) in combination with chemotherapies for treatment of patients with solid tumors.
Authors: Antonio Calles, Irene Brana, Patricia LoRusso, Lorrin Yee, Thomas Puchalski, Shobha Seetharam, Melan Balvers, Carla De Boer, Yusri A. Elsayed, Emiliano Calvo, Josep Tabernero
Journal: Journal of Clinical Oncology (2012)

3059 Background: CC-chemokine ligand 2 (CCL2) is expressed in various malignancies, implicated in angiogenesis, proliferation and metastasis. CNTO888 is a hIgG1κ mAb with selective high CCL2 binding affinity and showed preclinical antitumor activity. Methods: Primary objectives were safety and a recommended dose of CNTO 888 in combination with chemotherapy: Arm 1 - 15 mg/kg CNTO 888 + docetaxel 75 mg/m 2 Q3W; Arm 2 - 15 mg/kg CNTO 888 + gemcitabine 1000 mg/m 2 on D1 and 8 Q3W; Arm 3 - 15 mg/kg CNTO 888 + paclitaxel 175 mg/m 2 and carboplatin AUC6 Q3W; Arm 4 - 10 mg/kg CNTO 888 Q2W + pegylated doxorubicin 50 mg/m 2 Q4W. Two (Arms 1, 2, 3) or 4 (Arm 4) prior chemotherapies for advanced disease were allowed. Pharmacokinetic (PK) profile of CNTO 888 and chemotherapies, free and total CCL2, CTC/CEC count, and uNTX were evaluated. Adverse events (AE) and dose limiting toxicities (DLT) were evaluated after 6 subjects completed 1 cycle. Results: 53 subjects (22F/31M) were treated: Arm 1 n=15, Arm 2 n=12, Arm 3 n=12, Arm 4 n=14. Two DLTs occurred: a grade 4 febrile neutropenia (Arm 1) and a grade 3 neutropenia (Arm 2). All 4 combinations were found to be safe and tolerable and continued enrolment to a minimum of 12 subjects evaluable for safety and PK. Best overall response were partial response (PR) (1) and stable disease (18; 2 ≥ 4 months). One subject with pancreatic adenocarcinoma achieved PR, allowing for surgical resection. Most frequently reported (≥ 20%) related serious AEs are: Arm 1: Neutropenia, Stomatitis, Fatigue, Febrile neutropenia, Alopecia. Arm 2: Anemia. Arm 3: Thrombocytopenia, Alopecia, Neutropenia, Asthenia, Fatigue, Anemia, Arthralgia, Nausea, Vomiting. Arm 4: Stomatitis, Rash, Fatigue, Nausea, Anemia, Neutropenia. CNTO 888 did not affect the chemotherapy PK profile; similarly, chemotherapy did not affect the CNTO 888 PK profile. No subjects (n=38) tested positive for antibodies to CNTO 888. Free CCL2 declined 2 hrs post treatment and returned to baseline levels by 48 hrs and continued to increase with further administrations in all treatment arms. There were no consistent changes with other biomarkers. Conclusions: CNTO 888 in combination with standard chemotherapy was well tolerated but few objective responses were seen.
Prognostic impact of Del-1 expression in early breast cancer.
Authors: Soo Jung Lee, Yee Soo Chae, Jin Hyang Jung, Ji-young Park, Ho Yong Park, Jeeyeon Lee, Moon-Chang Baek
Journal: Journal of Clinical Oncology (2016)

e23263 Background: Del-1 on circulating extracellular vesicles was revealed as a promising diagnostic marker for breast cancer in our previous study. In the current study, we examined the prognostic impact of del-1 expression in tumor cells on prognosis in patients with early breast cancer (EBC). Methods: We compared Del-1 mRNA levels from breast epithelial cell line (MCF10A) and breast cancer cell lines (MDA-MB-231, MCF7, SK-BR3 and T-47D) performed by real-time PCR. Then, del-1 expression in breast cancer cells was investigated on the basis of the immunohistochemistry (IHC) of tissue microarray specimens from 417 EBC patients who underwent surgery between 2003 and 2008. We scored staining intensity (0 through 3) and analyzed association of del-1 expression with clinical/pathological characteristics and outcomes in patients with EBC Results: Del-1 mRNA was highly expressed in all breast cancer cell lines in particular MDA-MB-231 compared with MCF10A. A total of 329 (78.9%) patients were identified as Del-1 positive, and in particular higher expression rate of Del-1 was observed in HER2-positive EBC among TMA specimens (86.9% for HER2-overexpressed vs. 78.6% and 75.6% for hormone responsive and triple negative EBC, respectively; P = 0.016). However, no statistical difference in tumor characteristics and clinical outcomes including relapse and death were observed according to tumor expression of Del-1. Conclusions: Del-1 expression in breast cancer does not seem a prognostic marker for survival in patients with early breast cancer. However, higher expression rate of Del-1 in breast cancer cell identified in the current study compared with that of CEA or mammaglobin in previous studies suggests a new diagnostic marker for differential diagnosis of breast cancer involvement.
In Vivo Imaging Model of Multiple Myeloma and Its Cellular Interaction with the Bone Marrow Microenvironment
Authors: Judith Runnels, Alicia Carlson, Costas Pitsillides, Joel Spencer, Juwell Wu, Abdel kareem Azab, Aldo M. Roccaro, Anne-Sophie Moreau, Xavier Leleu, Andrew Kung, Scott J. Rodig, Kenneth C Anderson, Charles P. Lin, Irene M. Ghobrial
Journal: Blood (2008)
Pin1-Targeted Therapy for Systemic Lupus Erythematosus
Authors: Shuo Wei, Nobuya Yoshida, Greg Finn, Shingo Kozono, Morris Nechama, Vasileios C. Kyttaris, Xiao Zhen Zhou, George C. Tsokos, Kun Ping Lu
Journal: Arthritis & Rheumatology (2016)

Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease affecting multiple organs in the body, but therapeutic options are still very limited and often come with adverse effects. Increasing evidence has underlined an important role of the Toll-like receptor 7 (TLR-7)/TLR-9/interleukin-1 receptor-associated kinase 1 (IRAK-1)/interferon regulatory factor 7 (IRF-7) pathway in the development and progression of SLE. Notably, the prolyl isomerase Pin1 is an essential regulator of IRAK-1 in TLR-7/TLR-9 signaling, but its role in SLE is unknown. We undertook this study to determine whether Pin1 is activated and plays any role in the development and treatment of SLE.Activation of Pin1 and TLR-7/TLR-9/IRAK-1/IRF-7 signaling was determined in various cell types among peripheral blood mononuclear cells from healthy controls and SLE patients. The effects of Pin1 and TLR signaling on SLE development were determined using validated Pin1 short hairpin RNA (shRNA), Pin1 genetic knockout, and the small-molecule Pin1 inhibitor all-trans-retinoic acid (ATRA) in immune cells and in several strains of lupus-prone mice.We found abnormal activation of Pin1 and its downstream targets IRAK-1 and IRF-7 in SLE patients. Furthermore, inhibition of Pin1 using either validated Pin1 shRNA or ATRA blocked TLR-7-induced activation of IRAK-1 and IRF-7 in SLE patient-derived immune cells. Moreover, in multiple lupus-prone animals, both Pin1 knockout and ATRA strikingly attenuated the expression of autoimmunity, including skin lesions, lymphadenopathy, splenomegaly, glomerulonephritis, proteinuria, and production of anti-double-stranded DNA antibodies and CD4-CD8- T cells, and also prolonged overall survival in MRL/lpr and B6.lpr mice.Pin1 plays a critical role in the development of SLE, and Pin1-targeted therapy offers a promising new strategy for treating SLE.
Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells
Authors: Scott N. Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J. Hunt, John B. Schell, Katie Zeleski, Alison Yu, Cynthia R. Giver, Edmund K. Waller, Jeffrey S. Miller, Bruce R. Blazar, Leslie S. Kean
Journal: Blood (2016)
PTPS-23A NOVEL ROLE FOR NEUROTROPHIN SIGNALING IN PEDIATRIC ATYPICAL TERATOID RHABDOID TUMORS
Authors: Siobhan Pattwell, Tatsuya Ozawa, Gordana Juric-Sekhar, Eric Holland
Journal: Neuro-Oncology (2015)

Malignant rhabdoid tumors (MRTs) are among the most aggressive and lethal tumors in pediatric oncology, yet little is known about their underlying biology, prohibiting successful treatment outcomes. Aside from a commonly observed alteration in the SMARC1B tumor suppressor, these tumors are characterized by a remarkably high degree of genomic stability, suggesting that posttranslational modification, alternative splicing, or interactions with other tumor suppressors and growth factors may be involved. Attempts at modeling MRTs have proven difficult due to embryonic lethality of SMARC1B loss. One novel candidate for exploring MRT biology may lie within the neurotrophin family. Utilizing a unique approach employing the RCAS/TVA system - which allows for somatic transfer of genes into specific cell types - we have found that neurotrophin signaling influences the normative neurodevelopmental trajectory in wild-type mice when altered in nestin-positive cells. In the context of tumor suppressor loss (Ink4a/ARF deletion, PTEN loss), perturbations in neurotrophin signaling generate tumors that recapitulate the rhabdoid phenotype of a specific type of MRT found in the central nervous system, known as atypical teratoid rhabdoid tumor (AT/RT). In vivo analysis of downstream effectors such PI3K/Akt pathway targets, RhoA signaling, and transcription factors, further elucidate mechanistic links between neurotrophin signaling and AT/RT biology, while in vitro experiments quantify basic cellular functions implicated in tumorigenesis such as migration, proliferation, and apoptosis. Together these data uncover a novel role for neurotrophin signaling in AT/RT biology and may offer insight into therapeutic responses for treatments such as radiation and chemotherapy.
Reduction in CMV and Adenovirus Viremia after Haploidentical Donor Transplantation Utilizing CD45RA Depletion and NK Cell Infusion
Authors: Brandon M. Triplett, Bradley Muller, Guolian Kang, Shane J Cross, Joseph Moen, Mari H Dallas, Christine Hartford, William E. Janssen, Ping Law, Ewelina K. Mamcarz, David R Shook, Ashok Srinivasan, Randall T Hayden, Wing Leung
Journal: Blood (2015)
Patient Experience and Health Care Quality
Authors: Stephen Trzeciak, Anthony J. Mazzarelli
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
How to Integrate Elotuzumab and Daratumumab Into Therapy for Multiple Myeloma
Authors: Craig C. Hofmeister, Sagar Lonial
Journal: Journal of Clinical Oncology (2016)

Purpose Treatment options and outcomes for patients with multiple myeloma have dramatically improved over the past decade with new agents and drug targets for patients at all stages of disease. Incorporation of newly approved monoclonal antibodies is a clinical challenge because the trials used to gain approval are relatively limited in scope and may be less helpful for patients treated in the United States. This article will review data on the use of elotuzumab and daratumumab and provide a foundation for their use in current clinical practice. Methods We performed a review of current published articles and abstract data from clinical trials as well as data on managing adverse events. Results Single-agent activity was seen when using daratumumab in refractory myeloma, and trials for both elotuzumab and daratumumab have demonstrated significant activity when combined with proteasome inhibitors and immunomodulatory agents. Unique antibody-related adverse events and challenges are reviewed and discussed. Conclusion These antibodies already have had and will continue to have a dramatic impact on myeloma treatment. Combination therapy likely represents the best approach for their use, and trials that evaluate optimal timing and duration of therapy are in progress as part of induction, salvage, and maintenance therapy.
Association with programmed death ligand-1 (PDL-1) expression and Helicobacter Pylori infection in patients with non-diffuse type gastric carcinoma
Authors: M. Di Bartolomeo, A. Pellegrinelli, R. Iacovelli, F. Pietrantonio, R. Berenato, M. Caporale, M. Niger, M. Barbera, R. Labianca, A. Martoni, G. Rosati, D. Nitti, C. Boni, D. Amadori, M. Cantore, F. de Braud, E. Bajetta
Journal: Annals of Oncology (2015)
American Society of Anesthesiologist Classification—Higher Incentives for Higher Scores—Reply
Authors: Xiaoyu Nie, Soeren Mattke, Hangsheng Liu
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Expanded 3D Nanofiber Scaffolds: Cell Penetration, Neovascularization, and Host Response
Authors: Jiang Jiang, Zhuoran Li, Hongjun Wang, Yue Wang, Mark A. Carlson, Matthew J. Teusink, Matthew R. MacEwan, Linxia Gu, Jingwei Xie
Journal: Advanced Healthcare Materials (2016)

Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled size and thickness using a customized mold during the modified gas‐foaming process is reported. The expansion of nanofiber membranes is also simulated using a computational fluid model. Expanded nanofiber scaffolds implanted subcutaneously in rats show cellular infiltration, whereas non‐expanded scaffolds only have surface cellular attachment. Compared to unexpanded nanofiber scaffolds, more CD68 + and CD163 + cells are observed within expanded scaffolds at all tested time points post‐implantation. More CCR7 + cells appear within expanded scaffolds at week 8 post‐implantation. In addition, new blood vessels are present within the expanded scaffolds at week 2. The formed multinucleated giant cells within expanded scaffolds are heterogeneous expressing CD68, CCR7, or CD163 markers. Together, the present study demonstrates that the expanded nanofiber scaffolds promote cellular infiltration/tissue integration, a regenerative response, and neovascularization after subcutaneous implantation in rats. The use of expanded electrospun nanofiber scaffolds offers a promising method for in situ tissue repair/regeneration and generation of 3D tissue models/constructs.
Evidence from prospective cohort studies does not support current dietary fat guidelines: a systematic review and meta-analysis
Authors: Zoë Harcombe, Julien S Baker, Bruce Davies
Journal: British Journal of Sports Medicine (2016)

Objectives National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2016 systematic review examined the epidemiological evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. The present investigation extends our work by re-examining the totality of epidemiological evidence currently available relating to dietary fat guidelines. Methods A systematic review and meta-analysis of prospective cohort studies currently available, which examined the relationship between dietary fat, serum cholesterol and the development of CHD, were undertaken. Results Across 7 studies, involving 89 801 participants (94% male), there were 2024 deaths from CHD during the mean follow-up of 11.9±5.6 years. The death rate from CHD was 2.25%. Eight data sets were suitable for inclusion in meta-analysis; all excluded participants with previous heart disease. Risk ratios (RRs) from meta-analysis were not statistically significant for CHD deaths and total or saturated fat consumption. The RR from meta-analysis for total fat intake and CHD deaths was 1.04 (95% CI 0.98 to 1.10). The RR from meta-analysis for saturated fat intake and CHD deaths was 1.08 (95% CI 0.94 to 1.25). Conclusions Epidemiological evidence to date found no significant difference in CHD mortality and total fat or saturated fat intake and thus does not support the present dietary fat guidelines. The evidence per se lacks generalisability for population-wide guidelines.