tbuckley/cabot-search huggingface dataset:
Use of biomarkers and imaging to evaluate the treatment effect of AUY922, an HSP90 inhibitor, in patients with HER2+ or ER+ metastatic breast cancer.
Authors: C. P. Schroder, J. V. Pedersen, S. Chua, C. Swanton, M. Akimov, S. Ide, C. Fernandez-Ibarra, A. Dzik-Jurasz, E. De Vries, S. B. Gaykema, U. Banerji
Journal: Journal of Clinical Oncology (2011)

e11024 Background: Thorough biomarker assessments are increasingly considered vital for compounds in early clinical development to demonstrate proof of drug target modulation. HSP90 chaperones key client proteins that drive breast cancer (BC) including HER2, and estrogen receptor (ER). Inhibition of HSP90 leads to the degradation of these client proteins and induction of co-chaperones, such as HSP70. AUY922 is a highly potent, non-geldanamycin HSP90 inhibitor, and data from a Phase I study in patients with advanced solid tumors resulted in a recommended AUY922 Phase II dose of 70mg/m2. Patients with HER2+ or ER+ metastatic BC (mBC), who are refractory to standard treatment, have been enrolled into the ongoing Phase II part of the study, which includes a comprehensive biomarker evaluation to demonstrate the effect of AUY922 on key HSP90 client proteins. Methods: Single-agent AUY922 was administered by IV infusion 70 mg/m2 once a week in 28 day cycles to pts with HER2+ or ER+ BC. HSP70 and soluble HER2 (HER2-ECD) levels were quantitated by ELISA assays in peripheral blood mononuclear cells (PBMCs) and serum samples, respectively. Molecular imaging with FDG-PET and radiolabeled trastuzumab- or bevacizumab-PET (for HER2+ or ER+ mBC, respectively) was performed prior to, and during, treatment. Results: 10 pts have been treated to date (8 HER2+ and 2 ER+), and biomarker and imaging data are partially reported due to various technical and logistical challenges with each type of assessment. The maximum increase of HSP70 fold change ranged 1.9–10.4, with a median of 6.4 and mean of 5.9 fold, which is similar to previous observations. Soluble HER2 levels decreased ~45% and ~80% in 2 HER2+ patients who remained on study >5 cycles and both had partial metabolic responses by FDG-PET, and 1 had a confirmed partial response by RECIST as per investigator's assessment. In 3 pts, follow-up trastuzumab-PETs were assessable, indicating heterogeneous expression of HER2 in various lesions, and heterogeneous response in these lesions to therapy. Conclusions: AUY922 has shown preliminary activity in HER2+ or ER+ mBC and has demonstrated target modulation in keeping with its mechanism of action.
A pilot study of aerobic exercise performed in breast cancer patients during chemotherapy infusion.
Authors: D. Kerrigan, S. Keteyian, J. K. Ehrman, S. Brown, R. Filipiak, N. Martinez, D. Ihlenfeldt, J. Varga, E. M. Walker
Journal: Journal of Clinical Oncology (2010)

e19527 Background: Regular exercise mitigates some of the adverse side-effects (i.e. fatigue, nausea) in cancer patients receiving chemotherapy. Unfortunately, barriers such as access, motivation, and co-morbidities prevent many of these patients from beginning and adhering to exercise. To help facilitate exercise, this study describes the frequency of clinical events following a session of low level exercise cycle ergometry, performed while patients were simultaneously receiving their chemotherapy infusion. Methods: Breast cancer patients (n= 10, mean age=53, mean weight=92.2 kg, mean VO2= 19.7 ml kg−1 min−1) who were participating in the ExCITE (Exercise and Cancer Integrative Therapy and Education Program) trial at Henry Ford Hospital were offered the opportunity to perform mild exercise on a portable leg ergometry machine (Monarck) while receiving chemotherapy. This was in addition to a prescribed outpatient exercise program. Heart rate during infusion exercise was maintained approximately at 30-40% of heart rate reserve. All sessions were supervised by a clinical exercise physiologist. Differences in adverse clinical events following the infusion exercise session were compared to a standard infusion visit, in which no exercise occurred using a Pearson Chi- Square test. A chart review for significant clinical events occurring within 3 weeks of each infusion was performed by a nurse blinded to when exercise sessions occurred. Results: These 10 patients underwent 55 chemotherapy infusions; 18 conducted in conjunction with exercise and 37 without. Mean exercise duration = 16.4 minutes, mean work rate = 18 watts and mean heart rate = 24 beats above rest. Of those 18 infusion-exercise sessions, 2 adverse clinical events were reported within 3 weeks of the chemotherapy infusion (11%). In contrast, following standard chemotherapy sessions without exercise, adverse events were reported in 20 out of 37 visits (54%). This difference was significant (p = 0.002). Conclusions: These preliminary data indicate that performing mild exercise during chemotherapy infusion may be safe. However, further research is needed to determine if such an intervention might lessen chemotherapy-related clinical events. No significant financial relationships to disclose.
Outcomes Of Nonmyeloablative (NMA) Haploidentical Blood Or Marrow Transplantation (haploBMT) With High-Dose Posttransplantation Cyclophosphamide (PT/Cy) For Lymphoma
Authors: Yvette L. Kasamon, Javier Bolaños-Meade, Douglas Gladstone, Lode J. Swinnen, Jennifer A. Kanakry, Hua-Ling Tsai, Leo Luznik, Ephraim J. Fuchs, Richard J. Jones, Richard F. Ambinder
Journal: Blood (2013)
Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial.
Authors: Gabriel N. Hortobagyi, Allan Lipton, Helen K. Chew, William John Gradishar, Nicholas P. Sauter, Ramon W. Mohanlal, Ming Zheng, Beth McGrain, Catherine Van Poznak
Journal: Journal of Clinical Oncology (2014)

LBA9500^ Background: Zoledronic acid (ZOL, 4 mg) every (q) 4 wk reduces the risk of skeletal-related events (SREs) in patients (pts) with bone metastases from breast cancer (BC). The OPTIMIZE-2 trial examined whether ZOL q12 wk was non-inferior to ZOL q4 wk in pts who had previously received monthly IV bisphosphonate (BP) therapy for ~1 year or longer. Methods: This was a prospective, randomized, double-blind, multicenter trial in female pts with bone metastases from BC who previously received ≥9 doses of IV BP (ZOL or pamidronate) during the first 10-15 months of therapy. Pts were randomized (1:1) to receive ZOL 4 mg IV q4 wk or q12 wk (placebo between ZOL doses to maintain blind) for 1 year. The primary endpoint was the proportion of pts with ≥1 SRE on study (SRE rate). Primary analysis was non-inferiority (pre-defined margin of 10%) for the difference in SRE rates. Secondary endpoints included time to first SRE, skeletal morbidity rate (SMR), bone pain score, change in bone turnover markers, and safety. Results: 403 pts were randomized to ZOL q4 wk (n = 200) or q12 wk (n = 203). Median age was 59 years, and baseline characteristics were similar between arms. The SRE rate was 22% and 23.2% in the ZOL q4 and q12 wk arms, respectively. The difference in SRE rate between arms was 1.2% (95% CI, –7.5% to 9.8%; P = .724). The upper limit of this 95% CI (9.8%) is less than the predefined margin of 10%, which indicates non-inferiority of ZOL q12 wk vs q4 wk. Times to first on-study SRE (HR, 1.06; 95% CI, 0.70 to 1.60; P = .792) were similar in the ZOL q4 and q12 wk arms, and mean SMRs were also similar (0.46 vs 0.50, respectively; P = .854). Overall, changes from baseline in bone turnover markers, and the incidence of treatment-emergent adverse events (TEAEs), were similar in the 2 arms. Numerically more renal TEAEs were reported in the ZOL q4 wk vs q12 wk arm (9.6% vs 7.9%, respectively). Two cases (1.0%) of osteonecrosis of the jaw (ONJ) were reported in the q4 wk arm. Conclusions: Among pts who had received monthly IV BP therapy for 1 year or longer, the efficacy of continuing ZOL for an additional year at q12 wk was non-inferior to ZOL q4 wk. Fewer renal AEs and none of the ONJ events were observed in the ZOL q12 wk vs ZOL q4 wk arm. Clinical trial information: NCT00320710.
Vaccine skeptic pediatrician is charged with gross negligence
Authors: Owen Dyer
Journal: BMJ (2016)

A pediatrician who has linked vaccines to autism and written a bestselling parents’ guide that proposes an “alternative” vaccine schedule faces potential loss of his license over his care of a patient.

Robert Sears wrote a doctors’ letter for a 2 year old boy recommending “no more routine childhood vaccines for the duration of his childhood.” But the Medical Board of California said that he had not properly examined the child and gave no clinical evidence or explanation to justify the exemption.

Sears is also charged with failing to carry out a neurological examination when the boy later presented complaining of headaches, after being hit on the head with a hammer by his father.

Sears’s notes from the April 2014 consultation record the history that he took from the boy’s …
P1-254: Efficacy of Zoledronic acid in Lung cancer with bone metastasis
Authors: Young-Chul Kim, Kyu-Sik Kim, In-Jae Oh, Jong-Pil Jung, Jun-Gwang Son, Taewon Jang, Maan-Hong Jung, Choon-Hee Son, Sung-Yong Lee, Sun-Young Kim, Eunjin Kim, Kwan-Ho Lee, Jeong-Seon Ryu
Journal: Journal of Thoracic Oncology (2007)
Chronic Myelogenous Leukemia– Initiating Cells Require Polycomb Group Protein EZH2
Authors: Huafeng Xie, Cong Peng, Jialiang Huang, Bin E. Li, Woojin Kim, Elenoe C. Smith, Yuko Fujiwara, Jun Qi, Giulia Cheloni, Partha P. Das, Minh Nguyen, Shaoguang Li, James E. Bradner, Stuart H. Orkin
Journal: Cancer Discovery (2016)

Tyrosine kinase inhibitors (TKI) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia-initiating cells (LIC) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs and required for colony formation and survival and cell-cycle progression of CML cell lines. A critical role for EZH2 is supported by genetic studies in a mouse CML model. Inactivation of Ezh2 in conventional conditional mice and through CRISPR/Cas9-mediated gene editing prevents initiation and maintenance of disease and survival of LICs, irrespective of BCR-ABL1 mutational status, and extends survival. Expression of the EZH2 homolog EZH1 is reduced in EZH2-deficient CML LICs, creating a scenario resembling complete loss of PRC2. EZH2 dependence of CML LICs raises prospects for improved therapy of TKI-resistant CML and/or eradication of disease by addition of EZH2 inhibitors.This work defines EZH2 as a selective vulnerability for CML cells and their LICs, regardless of BCR-ABL1 mutational status. Our findings provide an experimental rationale for improving disease eradication through judicious use of EZH2 inhibitors within the context of standard-of-care TKI therapy. Cancer Discov; 6(11); 1237-47. ©2016 AACR.See related article by Scott et al., p. 1248This article is highlighted in the In This Issue feature, p. 1197.
DNA Methyltransferases Modulate the Bystander Effect in Mouse Embryonic Stem Cells.
Authors: Rebecca E. Rugo, Michael W. Epperly, Darcy Franicola, Benjamin Greenberger, Paavani Komanduri, Hong Wang, Dominika M. Wiktor-Brown, Joel S. Greenberger, Bevin P. Engelward
Journal: Blood (2007)
Diffusion Hypoxia and/or Primary Mitochondrial Failure?
Authors: Christos Lazaridis
Journal: JAMA Neurology (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 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
Preliminary Findings from an Investigation of Zika Virus Infection in a Patient with No Known Risk Factors — Utah, 2016
Authors: Carolyn Brent, Angela Dunn, Harry Savage, Ary Faraji, Mike Rubin, Ilene Risk, Wendy Garcia, Margaret Cortese, Shannon Novosad, Elisabeth Raquel Krow-Lucal, Jacqueline Crain, Mary Hill, Annette Atkinson, Dallin Peterson, Kimberly Christensen, Melissa Dimond, J. Erin Staples, Allyn Nakashima
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On July 12, 2016, the Utah Department of Health (UDOH) was notified by a clinician caring for an adult (patient A) who was evaluated for fever, rash, and conjunctivitis that began on July 1. Patient A had not traveled to an area with ongoing Zika virus transmission; had not had sexual contact with a person who recently traveled; and had not received a blood transfusion, organ transplant, or mosquito bites (1). Patient A provided care over several days to an elderly male family contact (the index patient) who contracted Zika virus abroad. The index patient developed septic shock with multiple organ failure and died in the hospital on June 25, 2016. The index patient's blood specimen obtained 2 days before his death had a level of viremia approximately 100,000 times higher than the average level reported in persons infected with Zika virus (2). Zika virus infection was diagnosed in patient A by real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing on a urine specimen collected 7 days after symptom onset. In addition, a serum specimen collected 11 days after symptom onset, after patient A's symptoms had resolved, was positive for antibodies to Zika virus by Zika immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (MAC-ELISA) and had neutralizing antibodies detected by plaque-reduction neutralization testing (PRNT). Working with Salt Lake and Davis County Health Departments, UDOH requested assistance from CDC with an investigation to determine patient A's exposures and determine a probable source of infection.
P3-031: Antitumour antibodies delivered through airways in lung cancer
Authors: Agnes Maillet, Nicolas Congy-Jolivet, José Hureaux, Laurent Vecellio, Isabelle Valo, Stéphanie Lerondel, Hervé Watier, Patrice Diot, Gilles Thibault, Alain Lepape, Philippe Anthonioz, Etienne Lemarié, Nathalie Heuzé-Vourc'h
Journal: Journal of Thoracic Oncology (2007)
P3-064: Gefitinib (Gefitinat) in advanced non small cell lung cancer-a follow up observation in Indian patients
Authors: Digambar Behera, Ritesh Aggrawal, Ashutosh N. Aggarwal, Dheeraj Gupta, Surinder K. Jindal, Surech C. Sharma, Rakesh Kapoor
Journal: Journal of Thoracic Oncology (2007)
Phase III clinical trials of atezolizumab combined with chemotherapy in chemotherapy-naive patients with advanced NSCLC.
Authors: Vassiliki Papadimitrakopoulou, Federico Cappuzzo, Robert M. Jotte, Martin Reck, Tony Mok, Alan Sandler, Daniel Waterkamp, Shelley Coleman, Yasuo Sugitani, Mark A. Socinski
Journal: Journal of Clinical Oncology (2016)

TPS9103 Background: Standard therapy for advanced NSCLC consists of platinum (plat)-based doublet chemotherapy (chemo), bevacizumab (bev), pemetrexed (pem), targeted agents and PD-L1/PD-1–targeted immunotherapy. Atezolizumab (MPDL3280A; atezo) inhibits binding of PD-L1 to PD-1 and B7.1. A Phase Ib study of 1L atezo + chemo demonstrated promising efficacy regardless of PD-L1 expression, with acceptable safety. Bev may further enhance atezo efficacy by inhibiting VEGF-related immunosuppression. Four Phase III randomized, multicenter, open-label studies are evaluating 1L therapy with atezo + plat-based chemo ± bev, or atezo + pem, in chemo-naive pts with advanced NSCLC (Table). Methods: Eligible pts must have previously untreated stage IV NSCLC, measurable disease per RECIST v1.1 and ECOG PS 0-1; pts with untreated CNS metastases, autoimmune disease or prior immunotherapy will be excluded. Archival tumor or biopsy sample will be obtained at screening. Stratification factors include sex, presence of liver metastases and PD-L1 expression. In IMpower130, 131 and 150, pts will be randomized to receive atezo 1200 mg with standard plat-based chemo ± bev (bev in IMpower150 only) for 4 or 6 21-day cycles, then maintenance with atezo. In IMpower132, pts will receive atezo + plat-based chemo + pem, then maintenance with atezo + pem. Endpoints include OS, PFS, ORR, DOR, safety, PK and QOL. Tumor biopsies at RECIST progression will be evaluated to distinguish pseudoprogression/tumor-immune infiltration from actual progression and to evaluate biomarkers associated with response and immune escape. Clinical trial information: NCT02367781, NCT02367794, NCT02657434, NCT02366143.Trial Name Histology Planned Enrollment Experimental Arm Comparator Arm Identifier IMpower130 Non-squamous 550 Atezo + carboplatin + nab-paclitaxel Carboplatin + nab-paclitaxel NCT02367781 IMpower131 Squamous 1200 Atezo + carboplatin + paclitaxel Atezo + carboplatin + nab-paclitaxel Carboplatin + nab-paclitaxel NCT02367794 IMpower132 Non-squamous 680 Atezo + carboplatin/cisplatin + pem Carboplatin/cisplatin + pem NCT02657434 IMpower150 Non-squamous 1200 Atezo + carboplatin + paclitaxel Atezo + carboplatin + paclitaxel + bev Carboplatin + paclitaxel + bev NCT02366143
TransComb: genome-guided transcriptome assembly via combing junctions in splicing graphs
Authors: Juntao Liu, Ting Yu, Tao Jiang, Guojun Li
Journal: Genome biology (2016)

Transcriptome assemblers aim to reconstruct full-length transcripts from RNA-seq data. We present TransComb, a genome-guided assembler developed based on a junction graph, weighted by a bin-packing strategy and paired-end information. A newly designed extension method based on weighted junction graphs can accurately extract paths representing expressed transcripts, whether they have low or high expression levels. Tested on both simulated and real datasets, TransComb demonstrates significant improvements in both recall and precision over leading assemblers, including StringTie, Cufflinks, Bayesembler, and Traph. In addition, it runs much faster and requires less memory on average. TransComb is available at http://sourceforge.net/projects/transcriptomeassembly/files/ .
LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells
Authors: Almut Brand, Katrin Singer, Gudrun E. Koehl, Marlene Kolitzus, Gabriele Schoenhammer, Annette Thiel, Carina Matos, Christina Bruss, Sebastian Klobuch, Katrin Peter, Michael Kastenberger, Christian Bogdan, Ulrike Schleicher, Andreas Mackensen, Evelyn Ullrich, Stefan Fichtner-Feigl, Rebecca Kesselring, Matthias Mack, Uwe Ritter, Maximilian Schmid, Christian Blank, Katja Dettmer, Peter J. Oefner, Petra Hoffmann, Stefan Walenta, Edward K. Geissler, Jacques Pouyssegur, Andreas Villunger, André Steven, Barbara Seliger, Stephan Schreml, Sebastian Haferkamp, Elisabeth Kohl, Sigrid Karrer, Mark Berneburg, Wolfgang Herr, Wolfgang Mueller-Klieser, Kathrin Renner, Marina Kreutz
Journal: Cell Metabolism (2016)
Surveillance des agents pathogènes respiratoires et des syndromes grippaux par les médecins généralistes - Pays-Bas, hiver 1997-98
Authors: M. L.A. Heijnen, J W Dorigo-Zetsma, A I M Bartelds, B Wilbrink, M. J.W Sprenger
Journal: Eurosurveillance (1999)

Depuis 1970, l'Institut Neerlandais de soins de sante primaires (NIVEL) coordonne les activites d'un reseau de surveillance sentinelle auquel participent 43 cabinets de medecins generalistes. Ces cabinets couvrent 1% de la population hollandaise, soit un echantillon representatif de la population nationale en termes d'âge, de sexe, et de degre d'urbanisation (1). NIVEL utilise les donnees du reseau pour calculer, chaque semaine durant la saison d'hiver, l'incidence des syndromes grippaux. Le systeme a ete ameliore a la demande de NIVEL, par l'Institut National de Sante Publique et de l'Environnement (Rijksinstituut voor Volksgezondheid en Milieu - RIVM). Ainsi, depuis l'hiver 1992-93, il inclut l'isolement et la detection des virus a partir des prelevements naso-pharynges des patients presentant des infections aigues des voies respiratoires superieures (IRA), dont 62% en moyenne sont des syndromes grippaux.
P2-049: Cytochrome P450 expression in non-small cell lung cancer
Authors: Tsunehiro Oyama, Kenji Sugio, Hidetaka Uramoto, Takamitsu Onizuka, Teruo Iwata, Tadahiro Nozoe, Mitsuhiro Takenoyama, Takeshi Hanagiri, Toyohi Isse, Toshihiro Kawamoto, Kosei Yasumoto
Journal: Journal of Thoracic Oncology (2007)
Intracellular Trafficking Network of Protein Nanocapsules: Endocytosis, Exocytosis and Autophagy
Authors: Jinxie Zhang, Xudong Zhang, Gan Liu, Danfeng Chang, Xin Liang, Xianbing Zhu, Wei Tao, Lin Mei
Journal: Theranostics (2016)

The inner membrane vesicle system is a complex transport system that includes endocytosis, exocytosis and autophagy. However, the details of the intracellular trafficking pathway of nanoparticles in cells have been poorly investigated. Here, we investigate in detail the intracellular trafficking pathway of protein nanocapsules using more than 30 Rab proteins as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled protein nanoparticles were internalized by the cells mainly through Arf6-dependent endocytosis and Rab34-mediated micropinocytosis. In addition to this classic pathway: early endosome (EEs)/late endosome (LEs) to lysosome, we identified two novel transport pathways: micropinocytosis (Rab34 positive)-LEs (Rab7 positive)-lysosome pathway and EEs-liposome (Rab18 positive)-lysosome pathway. Moreover, the cells use slow endocytosis recycling pathway (Rab11 and Rab35 positive vesicles) and GLUT4 exocytosis vesicles (Rab8 and Rab10 positive) transport the protein nanocapsules out of the cells. In addition, protein nanoparticles are observed in autophagosomes, which receive protein nanocapsules through multiple endocytosis vesicles. Using autophagy inhibitor to block these transport pathways could prevent the degradation of nanoparticles through lysosomes. Using Rab proteins as vesicle markers to investigation the detail intracellular trafficking of the protein nanocapsules, will provide new targets to interfere the cellular behaver of the nanoparticles, and improve the therapeutic effect of nanomedicine.
Non-pathogenic antinuclear antibodies contribute to the clearance of apoptotic antigens released during TNFalpha blockade in spondyloarthritis (SPA)
Authors: Tineke Cantaert, L De Rycke, B Vandooren, E Kruithof, C Wijbrandts, F De Keyser, E Veys, P. P Tak, D Baeten
Journal: Annals of the Rheumatic Diseases (2007)
S-Dimethylarsinoglutathione (SGLU/ZIO101) Is a Novel Active Organic Arsenical That Displays a Unique Gene Expression Profile in Myeloma Cells.
Authors: Lawrence H. Boise, Alejo A. Morales, Claire R. Croutch, Delia Gutman, Robert Peter Gale, Kelvin P. Lee
Journal: Blood (2006)