tbuckley/cabot-search huggingface dataset:
Use of a comprehensive panel of biomarkers to predict response to a fluorouracil-oxaliplatin (mFOLFOX6) regimen in patients with metastatic colorectal cancer.
Authors: M. J. Lamas, G. Duran, E. Balboa, B. Bernardez, U. Anido, E. Gallardo, S. Candamio, F. Barros, A. Carracedo, R. Lopez
Journal: Journal of Clinical Oncology (2010)

e13504 Background: Polymorphisms in the metabolism, detoxification, or DNA-repair pathway genes have been proposed as predictors of response to 5-fluorouracil (5fu) and oxaliplatin. We have studied the predictive value of a set of germline genetic polymorphisms in metastatic colorectal cancer patients treated with m-FOLFOX6. Methods: 72 patients, 50 men (69.4%) and 22 women (30.6%), were included after signing an informed consent. Median age was 65.5 years (32-80). All of them received m- FOLFOX6. DNA was extracted from peripheral blood samples and genotyped by direct sequencing, SNAPshot and Multiplex PCR techniques. 8 polymorphisms within 6 genes were investigated: TS 5′UTR (VNTR + G/C), TS 3′UTR (TS1494del6); MTHFR C677T and A1298C; GSTP1 I105V; ERCC1 C118T; XPD L751G and XRCC1 A399G. Association was evaluated by univariate analysis, and survival by Cox regression and Kaplan Meier. Results: The sample was in Hardy-Weinberg equilibrium. Only XPD-751 A/C was found to be significantly associated with a favorable progression-free survival (PFS). Median PFS for XPD-751 A/C patients (n=33) was 15.8 months (95% CI, 8.9–22.8), 9.7 (95% CI, 6.8–12.7) for C/C (n=11) and 7.5 months (95% CI, 4.5-10.5) for A/A (n=28), p=0.024. The risk of progression was: HR=1.93 (95% CI, 1.13-3.30; p=0.016) for A/A and HR=2.1 (95% CI, 1.02-4.29; p=0.042) for C/C. Patients with one or two -6bp alleles of TS-3′UTR tended to a lower risk of progression compared to +6bp/+6bp homozygotes, p=0.294. When analyzed jointly XPD-751 and TS-3′UTR, patients with two favorable genotype, A/C + -6bp, (n=16) showed a longer median PFS: 15.8 months (95% CI, 10.8 – 20.8) compared to 8.8 (95% CI,6.3-11.2) with one (n=40) and 7.4 months (95% CI,3-11.9) with none favorable genotype (n=16), p=0.028. The risk of progression was HR=1.75 (95% CI 0.93-3.29; p=0.080) and HR=2.69 (95% CI, 1.28-5.66; p=0.009) for patients with one o none favorable polymorphisms, respectively. Conclusions: In metastatic colorectal cancer patients treated with mFOLFOX6 the polymorphism XPD-751 Lys751Gln (A/C) was associated with increased PFS and the haplotype XPD-751/TS -6bp seems to predict the risk of progression. No significant financial relationships to disclose.
Efficacy of Reduced-Intensity Allogeneic Stem Cell Transplant after Brentuximab Vedotin in Patients with Hodgkin Lymphoma Relapsed after Autologous Transplant
Authors: Francesco Zallio, Alessandro Busca, Nicola Mordini, Maria jose Fornaro, Benedetto Bruno, Gioacchino Catania, Flavia Salvi, Guido Parvis, Marco Ladetto, Massimo Pini
Journal: Blood (2014)
Histological examination confirms clinical clearance of actinic keratoses following treatment with ingenol mebutate 0·05% gel
Authors: M. Ulrich, U. Reinhold, T. Skov, R. Elvang Søndergaard, P. Guitera
Journal: British Journal of Dermatology (2016)

BackgroundTo date, studies with ingenol mebutate gel have used clinical clearance, not histological clearance, as a primary efficacy endpoint.
The role of cultural group selection in explaining human cooperation is a hard case to prove
Authors: Ruth Mace, Antonio S Silva
Journal: Behavioral and Brain Sciences (2016)

Abstract We believe cultural group selection is an elegant theoretical framework to study the evolution of complex human behaviours, including large-scale cooperation. However, the empirical evidence on key theoretical issues – such as levels of within- and between-group variation and effects of intergroup competition – is so far patchy, with no clear case where all the relevant assumptions and predictions of cultural group selection are met, to the exclusion of other explanations.
NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20
Authors: Michael B. Drennan, Srinath Govindarajan, Eveline Verheugen, Jonathan M. Coquet, Jens Staal, Conor McGuire, Tom Taghon, Georges Leclercq, Rudi Beyaert, Geert van Loo, Bart N. Lambrecht, Dirk Elewaut
Journal: The Journal of Experimental Medicine (2016)

Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells.
Authors’ reply to Henderson
Authors: Maryam S Farvid, Walter C Willett, A Heather Eliassen
Journal: BMJ (2016)

We appreciate the comments on our study raised by readers of The BMJ .1 As our article acknowledged,2 recall of adolescent diet as an adult will be affected by measurement error, relying primarily on memory. We were unable to conduct ideal validation study of the high school dietary questionnaire—that is, collecting detailed weighed dietary records and biomarkers from high school …
The Chromosomal Abnormalities Del(17p), t(4;14), and +1q21 Predict Progression From Smoldering to Symptomatic Multiple Myeloma
Authors: Kai Neben, Anna Jauch, Thomas Hielscher, Jens Hillengass, Nicola Lehners, Marc S Raab, Anthony D. Ho, Hartmut Goldschmidt, Dirk Hose
Journal: Blood (2012)
Inhibition of lanthanide nanocrystal-induced inflammasome activation in macrophages by a surface coating peptide through abrogation of ROS production and TRPM2-mediated Ca2+ influx
Authors: Han Yao, Yunjiao Zhang, Liu Liu, Youcui Xu, Xi Liu, Jun Lin, Wei Zhou, Pengfei Wei, Peipei Jin, Long-Ping Wen
Journal: Biomaterials (2016)
Atorvastatin for Acute Coronary Syndromes
Authors: Anthony S. Wierzbicki
Journal: JAMA (2001)

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
Hepatopulmonary Shunt Reduction With 177Lu-DOTATATE Therapy
Authors: Emine Acar, Gamze Çapa Kaya, Hatice Durak
Journal: Clinical Nuclear Medicine (2016)

A 72-year-old man was diagnosed with well-differentiated neuroendocrine tumor of unknown primary with liver metastasis. All liver lesions were detectable only on Ga-DOTATATE PET/CT and were negative on F-FDG PET/CT. Intrahepatic Y radioembolization therapy was planned, but the hepatopulmonary shunt fraction was found to be 31.6%. Because the hepatopulmonary shunt fraction greater than 20% is an absolute contraindication to radioembolization, we decided to give him Lu-DOTATATE therapy. He received 4 courses of Lu-DOTATATE and showed regression in posttherapy Ga-DOTATATE PET/CT imaging. The hepatopulmonary shunt fraction was reduced to 8% after Lu-DOTATATE therapy.
Hematologic toxicity with adjuvant docetaxel and cyclophosphamide in early breast cancer.
Authors: F. N. Santos, M. R. Cruz, L. Cezana, L. A. Costa, C. A. de Azevedo, M. J. De Barros E Silva, L. L. Cezário, A. M. Alencar, M. F. Fanelli
Journal: Journal of Clinical Oncology (2010)

e11081 Background: After the results of docetaxel and cyclophosphamide (TC) superiority over doxorubicin and cyclophosphamide (AC) scheme, TC has been adopted at the A. C. Camargo Cancer Hospital as an option for adjuvant chemotherapy to early-breast cancer patients. However we have noticed a high rate of febrile neutropenia with this schedule. Methods: We conducted a retropective analysis of all patients with early breast cancer submitted to adjuvant chemotherapy with docetaxel 75 mg/m2 plus cyclophosphide 600 mg/m2, between January 2008 and July 2009, at A. C. Camargo Hospital in São Paulo-SP, Brazil. Primary end-point was to evaluate the rate of febrile neutropenia. Results: We have treated 30 women with TC. Median age was 55.7 years (33 to 76 years old). With regards to histologic caracteristics 58.6% were T1, 37.9% were T2, with a median tumor size of 16 mm; 6.9% had macroscopic positive axilar node; 65.5% patients were hormone receptor positive, 13.8% were HER2/neu positive. There was a total of 118 cycles of TC and we had 41.9% (n = 12) of patients with grade 3 or 4 neutropenia, and 31% (n = 9) needed hospitalization for febrile neutropenia (FN). Two patients initated TC with primary prophylaxis with growth factor. When we analysed only the first cycle, we found that 20.9% (n = 6) of patients had FN. After the first event, the use of secundary prophylaxis was initiated in all patients (n = 7) and there was still two further hospitalization for NF. One of them had dose reduction. Mean time of filgrastim 300 mcg/d administration was 5 days. We had no death related to FN. Ninety-three percent of all patients completed the treatment programmed. Conclusions: We have found a higher rate of FN with hospitalization (31%), in contrast with the hematologic toxicity reported preveously by US Oncology Group. The use of growth factor was able to prevent most of further hospitalization and mantain dose-intensity. G-CSF prophylaxis should be used in patients receiving adjuvant TC. No significant financial relationships to disclose.
Initiating a lymphedema screening program for breast cancer patients: Determining variability as a first step towards standardization.
Authors: Simona Flora Shaitelman, Susan E Ferguson, Sarah Marie DeSnyder, Parviz Kheirkhah, Susan Lilly, Marigold Travis, Theresa Johnson, Ana Alvarez, Duke Rohe, Thomas A. Buchholz, Isabelle Bedrosian
Journal: Journal of Clinical Oncology (2016)

267 Background: Breast cancer-related lymphedema (BCRL) is a known morbidity from treatment, and yet published estimates of its incidence are highly variable. Typically, a single volume measurement is recorded and the degree of intra-rater variability undefined. A threshold 5% limb volume change over time is used to define “mild lymphedema.” Therefore, small variations in volume measurements could substantially lead to over or under-diagnosis of BRCL. Gage R&amp;R is a measurement systems analysis tool that quantifies the amount of variability induced in measurements by the measurement system itself and compares this to the total variability observed. The objective of this study was to define the degree of variability in perometer arm volume measurements and factors contributing to this. Methods: A medical assistant (MA) was trained by a certified lymphedema therapist (CLT) to perform perometer-based lymphedema screening in the MD Anderson Nellie B. Connally Breast Center. Three measurements of each arm were taken and intra-rater variability against the mean calculated. Gage R&amp;R testing was performed by the MA and CLT, to determine the degree of repeatability and reproducibility variation. As a part of this analysis, 30 patients had both their left and right arm volume measured 3 times by each measurer. Results: Over 6 months, 565 breast cancer patients had preoperative BCRL screening by the MA, with an overall intra-rater variability of 2.2%. Among the 30 patients in the Gage R&amp;R study, median body mass index (BMI) was 27.7 (range 19.7-38.3), median height 1.61m (range 1.52-1.73m), intrarater variability of the MA was 2.07% and of the CLT was 1.21%. Gage R&amp;R accounted for 4.77% of total variability, 1.26% repeatability and 3.51% reproducibility. Regression analysis demonstrated that patient BMI and height impacted variability in measurements (R 2 = 16.27). Conclusions: Intra-rater variability for perometer arm measurements diminishes with experience. Gage R&amp;R variability is acceptable per industry standards, but there is room for improvement. Our findings suggest a role for targeted interventions to minimize variability in the diagnosis of BCRL based on patient characteristics.
Characterization of a Human Monoclonal Antibody Directed Against the Spacer Domain of ADAMTS13; a Prototype of Antibodies Present in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
Authors: Brenda M. Luken, Ellen A.M. Turenhout, Paul H.P. Kaijen, Johanna A. Kremer Hovinga, Jan A. Van Mourik, Rob Fijnheer, Jan Voorberg
Journal: Blood (2006)
Open data in drug discovery and development: lessons from malaria
Authors: Timothy N. C. Wells, Paul Willis, Jeremy N. Burrows, Rob Hooft van Huijsduijnen
Journal: Nature Reviews Drug Discovery (2016)

There is a growing consensus that drug discovery thrives in an open environment. Here, we describe how the malaria community has embraced four levels of open data - open science, open innovation, open access and open source - to catalyse the development of new medicines, and consider principles that could enable open data approaches to be applied to other disease areas.
Commentary on “Proteasome Inhibitors: A Novel Class of Potent and Effective Antitumor Agents”
Authors: Kenneth D. Tew
Journal: Cancer Research (2016)

The relatively recent clinical success of bortezomib, particularly in multiple myeloma, has established the validity of the proteasome as a viable target for anticancer drug development. This highly cited 1999 Cancer Research article from Adams and colleagues was published during the period when this drug was transitioning from preclinical studies to phase I clinical trial status. Their results detail structure-activity analyses using a series of boronic acid proteasome inhibitors and correlate cytotoxicity with inhibition of proteasome activity. In and of itself, the recognition that interference with proteasome functions represented a novel therapeutic approach likely underlies the popularity of this article. In addition, the provision of in vitro (at that time using the NCI 60 cell line panel) and in vivo antitumor activity, toxicology, and mouse pharmacokinetic and pharmacodynamic data provided a solid basis for establishing the future credentials for bortezomib to gain initial FDA approval in 2003. Cancer Res; 76(17); 4916-7. ©2016 AACRSee related article by Adams et al., Cancer Res 1999;59:2615-22Visit the Cancer Research 75(th) Anniversary timeline.
GBAS as a novel regulator for targeting centrosome amplification and malignant behavior in bladder cancer.
Authors: Hiroaki Matsumoto, Nakanori Fujii, Keita Kobayashi, Ryo Inoue, Yoshiaki Yamamoto, Kazuhiro Nagao, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2016)

429 Background: It has been reported that centrosome amplification (CA) facilitate to enhance the malignant potential and poor prognosis in bladder cancer. Besides Aurora A kinase drives CA, many studies suggest that inhibition of Aurora A is promising approach to concur invasive bladder cancer. We assess the novel molecule that is potential regulator of CA in bladder cancer. Methods: From 2000 to 2008, 57 bladder cancer patients treated in our hospital were included in this study. We obtained tumor sample by TUR or radical cystectomy with informed consent. We evaluated status of CA by fluorescent immuno-cytochemistry using anti pericentrin antibody. Then we performed array CGH to clarify hyper amplification gene in CA patients. By another approach, we identified candidate micro RNAs targeting Aurora A by miRNA tip array using CA+ or CA- bladder cancer cell lines. We performed pathway analysis to investigate potential target for CA regulated genes by both strategy. Finally, we found GBAS gene as a potential regulator for CA. Then, we assessed the function of GBAS gene by repressing or overexpressing in vitro and the status of GBAS expression by immunohistochemistry in tumor sample. Results: In CA- cell lines, GBAS overexpression increased CA rate compared with mock cells. Contrary, GBAS knock down reduced CA rate in CA+ cells. Also, in WST-1 assay, GBAS knock down repressed CA+ cell proliferation. While, GBAS overexpression facilitated migration and invasion in CA- cells. By western blot analysis, GBAS overexpression increased Aurora A expression, while GBAS suppression decreased that expression. GBAS knock down also repressed p53 expression in J82 cells. In immunohistochemistry, the patients with high GBAS expression were significant worse cancer specific survival compared with those of low expression (p &lt; 0.0001). Conclusions: These results suggest that GBAS gene could be a potential regulator of centrosome duplication via Aurora A expression in bladder cancer. Regulation of GBAS is providing pre-clinical proof-of-principle as promising approach for invasive bladder cancer.
Normal-Weight Central Obesity and Mortality Risk
Authors: Yan Yu
Journal: Annals of Internal Medicine (2016)

Letters16 August 2016Normal-Weight Central Obesity and Mortality RiskYan Yu, PhDYan Yu, PhDFrom Australian National University, Canberra, Australian Capital Territory, Australia.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0074 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Sahakyan and colleagues (1) analyzed NHANES III (Third National Health and Nutrition Examination Survey) (1988 to 1994) to examine mortality risk associated with body mass index (BMI) and waist-to-hip ratio (WHR). The Results section states that "WHR, but not BMI, was associated with high mortality risk after including both variables in the model," and the abstract states that "persons with normal-weight central obesity had the worst long-term survival." These statements are not compatible. If BMI were not associated with mortality risk, then persons who are normal-weight (based on BMI) but centrally obese (based on WHR) should not ...References1. Sahakyan KR, Somers VK, Rodriguez-Escudero JP, Hodge DO, Carter RE, Sochor O, et al. Normal-weight central obesity: implications for total and cardiovascular mortality. Ann Intern Med. 2015;163:827-35. [PMID: 26551006]. doi:10.7326/M14-2525 LinkGoogle Scholar2. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303:235-41. [PMID: 20071471] doi:10.1001/jama.2009.2014 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Australian National University, Canberra, Australian Capital Territory, Australia.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0074. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNormal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality Karine R. Sahakyan , Virend K. Somers , Juan P. Rodriguez-Escudero , David O. Hodge , Rickey E. Carter , Ondrej Sochor , Thais Coutinho , Michael D. Jensen , Véronique L. Roger , Prachi Singh , and Francisco Lopez-Jimenez Normal-Weight Central Obesity and Mortality Risk Rickey E. Carter , David O. Hodge , and Francisco Lopez-Jimenez Metrics Cited byStatus and transition of normal-weight central obesity and the risk of cardiovascular diseases: A population-based cohort study in ChinaMagnitude and predictors of normal-weight central obesity– the AWI-Gen study findings 16 August 2016Volume 165, Issue 4Page: 298KeywordsBody mass indexConflicts of interestDeath ratesDisclosureHealth surveysMorbid obesityMortalityNutritionObesityOverweight ePublished: 16 August 2016 Issue Published: 16 August 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Minor Subclones Harboring Small Insertions and Deletions Probably Due To Aberrant Splicing Can Frequently Be Detected By Deep Sequencing of The BCR-ABL Kinase Domain
Authors: Caterina De Benedittis, Simona Soverini, Katerina Machova Polakova, Adela Brouckova, Fausto Castagnetti, Gabriele Gugliotta, Francesca Palandri, Cristina Papayannidis, Hana Klamova, Paola Bresciani, Marzia Salvucci, Gianni Binotto, Tamara Intermesoli, Ilaria Iacobucci, Claudia Venturi, Mario Luppi, Emanuela Ottaviani, Maria Teresa Bochicchio, Manuela Mancini, Elisa Leo, Torsten Haferlach, Alexander Kohlmann, Domenico Russo, Gianantonio Rosti, Michele Baccarani, Michele Cavo, Giovanni Martinelli
Journal: Blood (2013)