tbuckley/cabot-search huggingface dataset:
Breast-GPA and type of treatment predictors of survival in brain metastasis patients.
Authors: Jenniffer Linares Aceituno, Agostina Stradella, Sonia Pernas Simon, Ana Ortega Franco, Valentín Navarro-Perez, Manuel Galdeano, Noemi Vidal Sarro, Roser Velasco, Miquel Macia Garau, Idoia Morilla, Ana Lucas Calduch, Adela Fernandez, Catalina Falo Zamora, Sabela Recalde, Miguel J. Gil Gil
Journal: Journal of Clinical Oncology (2016)

e13530 Background: brain metastases (BM) occur in 15-30% of patients with metastatic breast cancer (MBC). In spite of improvements in the treatment, the development of BM is still being a major limitation of life expectancy and quality of life for many patients (P). Methods: ambispective analysis of MBC patients who developed single or multiple BM and were treated in a single cancer comprehensive center. Identification of patients and updates of follow up were performed through Radiation Oncology department registries and Pathology Records. Breast Graded Prognostic Assessment (GPA) was calculated according to Sperduto GPA (2012). Results: from 2007 to 2014, 133 patients were identified; 30(22.6%) were diagnosed at de novo IV stage. Median age at BM diagnosis 52.3 years (29.7-81); 53 (39.8%) were luminal (LT), 42 (31.6%) HER2 positive (Her2), 31 (23.3%) triple negative (TN) and 7 cases unknown. Median PFS was 28m and median time to BM after cancer diagnosis (TBM) was 41 m (71m in LT, 26m in Her-2 and 20 m in TN (p < 0.001). Her2 showed more incidence of BM as first relapsed (17.5%) than others subtypes (11.1 % LT and 13.5% TN p = 0.002). 45 P (33.8%) had a solitary BM, 50 (36.7%) had 2-3 lesions and 35 (26.3%) more than 3, and 3 unknown. No correlation between number of lesions and histological subtypes was found. Breast-GPA: (0-1): 12%, (1.5-2): 26.3%, (2.5-3): 24.6% and (3.5-4): 25.6%. 18% were treated with stereotactic radiosurgery (SRS), 21% surgery (S) and 76% WBRT. Median survival after BM (BMS) was 12 m (7-17). BMS according GPA was (0-1) 8m, (1.5-2) 6m, (2.5-3) 19m and (3.5-4) 30m (p = 0.001). BMS according number of BM: 1 lesion 21m (8.9-33), 2-3 lesions 10 m (5.7-14) and > 3 lesions 8 m (5-11) and according subtypes LT 11 m (4-18),TN 8m (4.5-11.5) and Her2 26m (7-45). Local treatment with SRS and S prolonged BMS (28 vs 8 m p = 0.001) as well as the administration of chemotherapy (29 vs 10 m p = 0.032). Significant prognostic factors by multivariate Cox regression were GPA (HR 0.7 CI 0.55-0.91 p = 0.008) and number of lesions (HR 1.3 CI 1.03-1.79 p = 0.027). Conclusions: Breast-GPA, number of lesions and type of treatment are the most important prognosis factors for MBC patients with BM. Multidisciplinary treatment should be decided according to these factors.
Evidence Implicating Immunological Host Effects in the Efficacy of Metronomic Low-Dose Chemotherapy
Authors: Yuval Shaked, Elizabeth Pham, Santosh Hariharan, Ksenia Magidey, Ofrat Beyar-Katz, Ping Xu, Shan Man, Florence T.H. Wu, Valeria Miller, David Andrews, Robert S. Kerbel
Journal: Cancer Research (2016)

Abstract Conventional chemotherapy drugs administered at a maximum tolerated dose (MTD) remains the backbone for treating most cancers. Low-dose metronomic (LDM) chemotherapy, which utilizes lower, less toxic, doses given on a close regular basis over prolonged periods, is an alternative and better tolerated potential strategy to improve chemotherapy. LDM chemotherapy has been evaluated preclinically and clinically and has shown therapeutic benefit, in both early and advanced stage metastatic disease, especially when used as a maintenance therapy. However, knowledge about the antitumor mechanisms by which LDM chemotherapy acts remain limited. Here we characterized the effects of LDM and MTD capecitabine therapy on tumor and host cells using high-throughput systems approaches involving mass spectrometry flow cytometry and automated cell imaging followed by in vivo analyses of such therapies. An increase in myeloid and T regulatory cells and a decrease in NK and T cytotoxic cells were found in MTD–capecitabine–treated tumors compared with LDM-capecitbine-treated tumors. Plasma from MTD capecitabine-treated mice induced a more tumorigenic and metastatic profile in both breast and colon carcinoma cells than plasma from mice treated with LDM capecitabine. These results correlated, in part, with in vivo studies using models of human or mouse advanced metastatic disease, where the therapeutic advantage of MTD capecitabine was limited despite a substantial initial antitumor activity found in the primary tumor setting. Overall these results implicate a possible contribution of immunologic host effects in accounting for the therapeutic limitations of MTD compared with LDM capecitabine. Cancer Res; 76(20); 5983–93. ©2016 AACR.
HIV/AIDS in 2016 and Beyond
Authors: Robert Steinbrook
Journal: JAMA (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 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
An open-label, multi-center, phase 2 study of switch maintenance with TAS-102 plus bevacizumab following oxaliplatin or irinotecan-based fluoropyrimidine-containing induction chemotherapy in patients with metastatic colorectal cancer: ALEXANDRIA study.
Authors: Mohamed E. Salem, Hongkun Wang, Marwan Fakih, Sameh Mikhail, Brandon George Smaglo, Michael J. Pishvaian, Aiwu Ruth He, Louis M. Weiner, Tanios S. Bekaii-Saab, John Marshall
Journal: Journal of Clinical Oncology (2016)

TPS3624 Background: Maintenance therapy with a fluoropyrimidine plus bevacizumab is a widely accepted strategy in the treatment of mCRC, having been shown significant improvement in progression-free survival (PFS), predominantly in the CAIRO 3 study (Simkins LH, Lancet 2015). TAS-102 is a novel nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride. In the randomized phase 3 RECOURSE trial, TAS-102 demonstrated a significant improvement in overall survival (OS) and PFS, and resulted in a 44% disease control rate, compared with placebo in patients with refractory CRC. (Mayer RJ, NEJM 2015). Methods: ALEXANDRIA (NCT02654639) is an open-label, multicenter, single arm phase 2 study designed to evaluate efficacy and safety of switch maintenance with TAS-102 plus bevacizumab following induction chemotherapy in mCRC patients. Eligibility criteria include histologically confirmed mCRC, ECOG ≤ 1, acceptable organ and bone marrow function, and patients must have had 16 to 20 weeks of standard first line therapy with bevacizumab plus oxaliplatin- or irinotecan-containing regimens and have stable disease or better. Forty-five patients will be enrolled on the study to receive 35 mg/m2 TAS-102 po bid on Days 1-5 and Days 8-12 of each 28-day cycle. Bevacizumab, 5 mg/kg IV, will be administered every 14 days. This treatment cycle will be repeated every 28 days until patients demonstrate disease progression, experience unacceptable toxicity or withdraw consent. CT scans will be performed every 8 weeks. The primary endpoint is PFS, and secondary endpoints include OS, safety, ORR, DCR, TTP, and DDC. This study is designed to have 80% power (2-sided alpha level of 0.05) to test the median PFS of 8 mo vs. 5 mo (historical control) using a one-sample log-rank test. The time-to-event endpoints (PFS, OS, TTP, and DDC) will be estimated using the Kaplan-Meier method. Estimates of the rates (ORR and DCR) will be presented with their 95% confidence intervals. Clinical trial information: NCT02654639.
Cetylpyridinium chloride mouth rinses alleviate experimental gingivitis by inhibiting dental plaque maturation
Authors: Fei Teng, Tao He, Shi Huang, Cun-Pei Bo, Zhen Li, Jin-Lan Chang, Ji-Quan Liu, Duane Charbonneau, Jian Xu, Rui Li, Jun-Qi Ling
Journal: International Journal of Oral Science (2016)

Oral rinses containing chemotherapeutic agents, such as cetylpyridinium chloride (CPC), can alleviate plaque-induced gingival infections, but how oral microbiota respond to these treatments in human population remains poorly understood. Via a double-blinded, randomised controlled trial of 91 subjects, the impact of CPC-containing oral rinses on supragingival plaque was investigated in experimental gingivitis, where the subjects, after a 21-day period of dental prophylaxis to achieve healthy gingivae, received either CPC rinses or water for 21 days. Within-subject temporal dynamics of plaque microbiota and symptoms of gingivitis were profiled via 16S ribosomal DNA gene pyrosequencing and assessment with the Mazza gingival index. Cetylpyridinium chloride conferred gingival benefits, as progression of gingival inflammation resulting from a lack of dental hygiene was significantly slower in the mouth rinse group than in the water group due to inhibition of 17 gingivitis-enriched bacterial genera. Tracking of plaque α and β diversity revealed that CPC treatment prevents acquisition of new taxa that would otherwise accumulate but maintains the original biodiversity of healthy plaques. Furthermore, CPC rinses reduced the size, local connectivity and microbiota-wide connectivity of the bacterial correlation network, particularly for nodes representing gingivitis-enriched taxa. The findings of this study provide mechanistic insights into the impact of oral rinses on the progression and maturation of dental plaque in the natural human population.
Origin of the U87MG glioma cell line: Good news and bad news
Authors: Marie Allen, Mia Bjerke, Hanna Edlund, Sven Nelander, Bengt Westermark
Journal: Science Translational Medicine (2016)

Human tumor-derived cell lines are indispensable tools for basic and translational oncology. They have an infinite life span and are easy to handle and scalable, and results can be obtained with high reproducibility. However, a tumor-derived cell line may not be authentic to the tumor of origin. Two major questions emerge: Have the identity of the donor and the actual tumor origin of the cell line been accurately determined? To what extent does the cell line reflect the phenotype of the tumor type of origin? The importance of these questions is greatest in translational research. We have examined these questions using genetic profiling and transcriptome analysis in human glioma cell lines. We find that the DNA profile of the widely used glioma cell line U87MG is different from that of the original cells and that it is likely to be a bona fide human glioblastoma cell line of unknown origin.
The Dynamics of the Human Infant Gut Microbiome in Development and in Progression toward Type 1 Diabetes
Authors: Aleksandar D. Kostic, Dirk Gevers, Heli Siljander, Tommi Vatanen, Tuulia Hyötyläinen, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Päivi Pöhö, Ismo Mattila, Harri Lähdesmäki, Eric A. Franzosa, Outi Vaarala, Marcus de Goffau, Hermie Harmsen, Jorma Ilonen, Suvi M. Virtanen, Clary B. Clish, Matej Orešič, Curtis Huttenhower, Mikael Knip, Ramnik J. Xavier
Journal: Cell Host & Microbe (2016)
Overall survival (OS) analysis of a phase l trial of a vector-based vaccine (PSA-TRICOM) and ipilimumab (Ipi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Authors: R. A. Madan, M. Mohebtash, P. M. Arlen, M. Vergati, S. M. Steinberg, K. Y. Tsang, W. L. Dahut, J. Schlom, J. L. Gulley
Journal: Journal of Clinical Oncology (2010)

2550 Background: Therapeutic cancer vaccines have demonstrated great promise in the treatment of mCRPC. PSA-TRICOM is a vector-based vaccine that targets PSA and includes the transgenes for 3 human costimulatory molecules (ICAM-I, LFA-3, and B7.1) to enhance T-cell activation. A multicenter, randomized phase II trial demonstrated a significant OS advantage versus placebo in mCRPC. A smaller NCI phase II study demonstrated an association of OS with PSA-specific immune response (IR). CTLA-4 is a molecule expressed by activated T-cells and signaling through this turns off the IR. Preclinical models demonstrate that a blockade of CTLA-4 can enhance T-cell mediated IR to vaccine. Ipi is a monoclonal antibody that blocks the moderating effects CTLA-4. Methods: Patients (pts) with mCRPC were treated in this phase I, dose- escalation study. All pts received PSA-TRICOM on days 1, 15, 29 and then monthly. Ipi was administered at 1, 3, 5, or 10 mg/kg in sequential dose levels (DL) monthly. After 6 months (mos), pts could receive maintenance Ipi every 3 mos. Predicted OS was determined for each pt. Although the first 6 pts enrolled received prior chemotherapy, the remainder of pts enrolled were chemotherapy naive (CN). Results: The study has fully accrued 30 pts. Median on-study age was 69 years (range: 49–81); median PSA was 49 mcg/L (3–729), median Gleason score was 8 (4-10), and median PSA doubling time was 2.3 mos. The median time to radiographic progression for CN pts was 5.9 mos. The median Halabi predicted OS for all pts was 18.5 mos. The median OS for all pts was 31.8 mos with a 74% survival probability at 24 mos. The median OS for CN pts is 30.9 months. There was no significant difference in OS based on DL. 4 of 6 evaluable pts at the higher DLs had a greater than 2-fold increase in antigen-specific T-cell responses. Conclusions: Two phase II trials in CN mCRPC treated 114 pts with this same vaccine demonstrating an OS of ∼26 mos. These data suggest that the addition of immune checkpoint inhibition may augment the clinical benefit of vaccines. Additional, randomized trials are required to further investigate immune checkpoint inhibition and vaccine in mCRPC. No significant financial relationships to disclose.
Mental Stress–Induced Myocardial Ischemia Related to Generalized Anxiety Disorder in a Patient With Acute Coronary Syndrome and Normal Coronary Arteries
Authors: Julio Cesar Tolentino, Juliana J. Schmidt, Guilherme J. Schmidt, Claudio Tinoco Mesquita, Sergio L. Schmidt
Journal: Clinical Nuclear Medicine (2016)

Mental stress–induced myocardial ischemia (MSIMI) has been described in patients with acute coronary syndrome (ACS). We reported the case of a patient admitted with ACS and MSIMI related to generalized anxiety disorder (GAD). Myocardial perfusion imaging (MPI) after exercise stress and computed tomography coronary angiography showed normal results. In contrast, MPI with mental stress documented MSIMI. He began to improve 7 days after starting escitalopram and remained without angina at 1-year follow-up. These data suggest the applicability of mental stress radionuclide imaging for the detection of MSIMI in patients with ACS and GAD, even in normal coronary arteries.
GPs report missing payments for trainees’ pay
Authors: Abi Rimmer
Journal: BMJ (2016)

General practices across England have not received reimbursement for trainees’ salaries because of problems with the outsourcing company Capita, the BMA has said.

Practices in Berkshire, Buckinghamshire, Oxfordshire, Humberside, Nottinghamshire, Derbyshire, the North East, and Wessex have reported problems in receiving payments.

Krishna Kasaraneni, chair of the BMA’s GP education, training, and workforce subcommittee, explained that Capita was responsible for reimbursing general practices for the salaries of GP trainees that they directly employed after it took over the provision by Primary Care Support Services England (PCSE).

Kasaraneni said, “Since that function has moved to Primary Care Support Services England, which is essentially Capita, it has gone completely up in the air. So practices aren’t being told how much they need to be paying the trainees, and because the practices pay the trainees themselves they are paying the trainees, but what they are paying …
Scotland prioritises action on child poverty
Authors: Bryan Christie
Journal: BMJ (2016)

Scottish ministers are stepping up their efforts to eradicate child poverty after criticising the UK government for failing to prioritise the needs of low income families.

Legislation is set to be introduced in Scotland that will require ministers to deliver on targets to reduce child poverty. If the proposed targets were met by 2030 the proportion of children living in absolute poverty would fall from 21% at present to 5%.

The Child Poverty Bill planned for Scotland contrasts …
Reply to reviewers: Reuse, embodied interactivity, and the emerging paradigm shift in the human neurosciences
Authors: Michael L Anderson
Journal: Behavioral and Brain Sciences (2016)

Abstract In this reply to reviewers, I argue that, although reforming the taxonomy of psychology will lead to great insights in the cognitive sciences, it will not result in 1:1 structure-function mappings in the brain; we should expect to see a great deal of irreducible functional diversity in the brain at multiple spatial scales. I further clarify both the promise and the limitations of the analytic techniques for capturing functional diversity and interrogating the taxonomy of psychology; describe the ways in which neural reuse can help us understand human development; further explore the ways in which my proposals for integrating psychology, neuroscience, and evolutionary biology differ from the approach exemplified by contemporary evolutionary psychology; and lay out some new and hopefully interesting avenues for future research.
Musculoskeletal disease in Nepal: A countrywide cross-sectional survey on burden and surgical access
Authors: Sagar S. Chawla, Subrat Khanal, Pranita Ghimire, Neeraja Nagarajan, Shailvi Gupta, Varshini Varadaraj, Benedict C. Nwomeh, Adam L. Kushner
Journal: International Journal of Surgery (2016)
The Metabotropic Glutamate Receptor Subtype 1 Mediates Experience-Dependent Maintenance of Mature Synaptic Connectivity in the Visual Thalamus
Authors: Madoka Narushima, Motokazu Uchigashima, Yuki Yagasaki, Takeshi Harada, Yasuyuki Nagumo, Naofumi Uesaka, Kouichi Hashimoto, Atsu Aiba, Masahiko Watanabe, Mariko Miyata, Masanobu Kano
Journal: Neuron (2016)
Incorporating Patient Preferences in Evidence-Based Medicine—Reply
Authors: Murray Krahn
Journal: JAMA (2008)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
126P: Outcome after post-operative radiotherapy (PORT) in ypN2 or R1/R2 versus no PORT in ypN0 stage III-N2 non-small cell lung cancer after induction chemotherapy and resection
Authors: C. Billiet, S. Peeters, H. Decaluwé, J. Vansteenkiste, C. Dooms, C. Deroose, M. Hendrikx, C. Le Péchoux, J. Mebis, D. De Ruysscher
Journal: Journal of Thoracic Oncology (2016)
Analysis of progression-free survival in the new EPOC study in an “all wild-type” population.
Authors: John A. Bridgewater, Sian Alexandra Pugh, Karwan Moutasim, Gareth Thomas, Raphaële Thiébaut, Francois Liebaert, Stephen Falk, Meg Finch-Jones, Juan W. Valle, Derek O'Reilly, Ajith K. Siriwardena, Joanne Hornbuckle, Myrddin Rees, Tim Iveson, Tamas Hickish, O James Garden, David Cunningham, Tim Maughan, John Neil Primrose
Journal: Journal of Clinical Oncology (2014)

3566 Background: The phase 3 new EPOC study, randomised KRAS wild-type (WT) patients with resectable or suboptimally resectable colorectal cancer liver metastases (CRLM) 1:1 to receive chemotherapy with or without cetuximab before and after liver resection. The primary end point was progression free survival (PFS). The trial demonstrated a detriment in PFS following the addition of cetuximab to chemotherapy from 20.5 to 14.1 months. KRAS was determined using pyrosequencing in codons 12, 13, and 61 (HR 1·48 95% CI 1·04-2·12 p=0.03). Subsequently, benefit from epidermal growth factor inhibition was shown to be improved following restriction to an all RAS WT population in patients with advanced disease (Douillard NEJM 2013). We describe a further analysis of PFS in an all WT new EPOC population. Methods: Samples of tumor from the primary colorectal and liver resections were obtained. Patients were further analysed using MiSeq for KRAS (codon 12, 13, 61, 117 and 146), BRAF (V600E), NRAS (12, 13, 61, 117 and 146), PIK3CA (547 and 1047). Those without any mutation were classed as “all WT”. Additional qPCR was performed for MET, AREG, EREG, EGFR, HER2-4, PTEN and NT5E. Survival analyses were completed using the Kaplan-Meier method and the log-rank test. Results: To date 106 samples of primary tumor and 103 samples of CRLM have been analysed corresponding to 155 of the 236 KRAS WT patients. Further mutations were found in samples from 22 patients in the KRAS WT group (16 KRAS, 12 NRAS, 3 PIK3CA, and 6 BRAF mutations). Paired samples of primary tumour and CRLM were analysed for 47 patients. Three mutations were matched between the primary and corresponding CRLM, with the remaining 13 mutations (six in the primary tumor, seven in CRLM) not found in the paired sample. Analysis of PFS in the all WT population of patients previously included in the primary analysis (chemo alone arm n=48, chemo plus cetuximab arm n=54) demonstrated a similar trend in detriment in median PFS of 20.5 months to 16.4 months respectively (HR 1.34 95% CI (0.76-2.36) p = 0.32). Conclusions: The addition of cetuximab to chemotherapy and surgery for operable CRLM in KRAS wild-type patients results in an inferior PFS. More stringent selection of an all WT cohort does not significantly alter the detriment observed in the KRAS WT population. Clinical trial information: 22944367.