tbuckley/cabot-search huggingface dataset:
Notice of Retraction: Jamal SA, et al. Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial.
Authors: Richard Eastell, Celeste J. Hamilton, Steven R. Cummings
Journal: JAMA (2016)

To the Editor We wish to retract the article “Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial,”1 published in the February 23, 2011, issue of JAMA.

In a report issued by an investigating committee appointed by Women’s College Hospital, affiliated with the University of Toronto, to investigate, in part, the availability of data relative to this study, the committee concluded, based on objective evidence, that Dr Jamal had falsified and/or fabricated data and used that data for statistical analysis. Dr Jamal was both the first and corresponding author and was responsible for the integrity of the data and the accuracy of the data analysis. None of the other coauthors were involved in the misrepresentation of these data. All of the authors recognize the seriousness of this issue. We regret that the results of this study have been compromised and are committed to correcting the medical literature.
Abstract TMEM-027: TARGETING RGNEF (P190RHOGEF/ARHGEF28) IMPAIRS OVARIAN TUMOR INITIATION AND PROGRESSION
Authors: Elizabeth G. Kleinschmidt, Nichol L.G. Miller, Isabelle Tancioni, Denise C. Connolly, David D. Schlaepfer
Journal: Clinical Cancer Research (2017)

Abstract Rho GTPase regulatory and integrin signaling pathways are associated with poor high-grade serous ovarian carcinoma (HGSOC) patient survival1. Focal adhesion kinase (FAK) transmits signals from integrins and promotes HGSOC tumor progression through mechanisms involving tumor-stromal cell interactions2. We previously found that the Rho guanine nucleotide exchange factor Rgnef (also named p190RhoGEF or Arhgef28) activates FAK as well as RhoA GTPase activity in mouse fibroblasts3. Here we find that Rgnef protein expression is elevated in Stage 3-4 HGSOC and that Rgnef knockout prevents spontaneous ovarian tumor formation in the MISIIR-T-antigen (TAg) induced C57BL/6 mouse model. At 17 weeks, Rgnef-/-;TAg ovarian tumors were significantly smaller (p&amp;lt;0.001) than Rgnef+/+;TAg controls. Primary Rgnef-/-;TAg and Rgnef+/+;TAg tumor cells were isolated and expanded ex vivo. Although loss of Rgnef did not alter growth as 3D spheroids, Rgnef-/-;TAg orthotopic (ovarian bursa) and intraperitoneal tumors were significantly smaller (p&amp;lt;0.01) than Rgnef+/+;TAg tumors in MISIIR-TAg-Low C57BL/6 syngeneic mice. Notably, FAK activation (as measured by FAK Y397 phosphorylation) was decreased in Rgnef-/-;TAg ascites-associated tumor cells. Together, these studies show that Rgnef loss impedes tumor growth independently of stromal Rgnef status and supports the notion that an Rgnef-FAK signaling linkage facilitates ovarian tumor initiation and progression. 1.Zhang, H., et al. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer. Cell 166 (2016). 2.Sulzmaier, F.J., Jean, C. &amp; Schlaepfer, D.D. FAK in cancer: mechanistic findings and clinical applications. Nat. Rev. Cancer 14, 598-610 (2014). 3.Miller, N.L., et al. A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation. J. Cell Sci. 126, 5074-5085 (2013). Citation Format: Elizabeth G. Kleinschmidt, Nichol L.G. Miller, Isabelle Tancioni, Denise C. Connolly, David D. Schlaepfer. TARGETING RGNEF (P190RHOGEF/ARHGEF28) IMPAIRS OVARIAN TUMOR INITIATION AND PROGRESSION [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-027.
Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients
Authors: M.F. Sanmamed, J.L. Perez-Gracia, K.A. Schalper, J.P. Fusco, A. Gonzalez, M.E. Rodriguez-Ruiz, C. Oñate, G. Perez, C. Alfaro, S. Martín-Algarra, M.P. Andueza, A. Gurpide, M. Morgado, J. Wang, A. Bacchiocchi, R. Halaban, H. Kluger, L. Chen, M. Sznol, I. Melero
Journal: Annals of Oncology (2017)
Gestational Weight Gain and Outcomes for Mothers and Infants
Authors: Aaron B. Caughey
Journal: JAMA (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 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
Relationship of pathological features and a 21 gene expression assay in young women with early breast cancer.
Authors: Martin Boniface Gitobu Mutonga, Sedona Speedy, Regina Uthe, Kelly Kindy, Aisha Brownlee, Sarika Jain, William John Gradishar, Lisa E. Flaum, Cesar Augusto Santa-Maria
Journal: Journal of Clinical Oncology (2017)

e12050 Background: There is emerging evidence that a 21 gene expression assay recurrence score (RS) is prognostic independent of age. In practice, pathological markers may influence decision to recommend adjuvant chemotherapy. Methods: The primary objective of this study is to investigate the relationship between the RS and pathological markers between younger (29-49) and older (50-79) women with early stage ER+ breast cancer. Pathological markers investigated included the progesterone receptor (PR), grade, Ki-67, and P53. Patients who underwent 21 gene assay testing between 2002 through 2012 were sequantially identified. Data was extracted via the institutional tumor registry or chart reviewing. For each pathological feature, mean RS was compared between younger and older patients by t-tests. Trends in chemotherapy recommendation were assessed between younger and older patients within each RS risk category (≤10, 11-25, ≥26). Results: Between 2002 and 2012, 344 eligible patients were identified. 133 were ≤49 years of age, and 211 ≥50. There was no difference in distribution of RS across age (R 2 =3x10 -4 ). Between younger and older patients, there was no difference in mean RS for any pathological marker (table 1). Within each age group, mean RS was always higher in tumors that were PR negative, grade 2/3, Ki67 &gt;10%, and P53 ≥10% (p&lt;0.05, respectively). In patients with a RS ≤10, 0% were recommended adjuvant chemotherapy irrespective of age. In patients with a RS 11-25, 39% of younger and 40% of older women were recommended chemotherapy. In patients with a RS ≥26, 100% of younger and 98% of older women were recommended chemotherapy. Conclusions: The relationships between pathological features and RS are consistent across age, supporting observations that the RS can predict benefit irrespective of age. See table. [Table: see text]
A phase III, open label, prospective, randomized, multicenter, neoadjuvant study of chemotherapy versus endocrine therapy in premenopausal patient with hormone responsive, HER2 negative, breast cancer (KBCSG 012).
Authors: hee Jeong Kim, Woo Chul Noh, Eun Sook Lee, Leesu Kim, Yongsik Jung, Wonshik Han, Seok Jin Nam, Sei-Hyun Ahn
Journal: Journal of Clinical Oncology (2017)

517 Background: Neoadjuvant endocrine therapy has shown efficacy in hormone-responsive postmenopausal breast cancer patients. We aimed to assess the efficacy and safety of cytotoxic chemotherapy versus endocrine therapy for hormone-responsive lymph node-positive premenopausal breast cancer patients in a neoadjuvant setting. (NCT01622361). Methods: In this phase 3, randomized, double blind, parallel group, multicenter study, we enrolled premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with adriamycin plus cyclophosphamide (AC) followed by taxane (T) or neoadjuvant endocrine therapy with zoladex and tamoxifen. Results: 187 patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed the 24 week neoadjuvant treatment period (n=87, both). More patients in the chemotherapy group had a complete or partial response than did those in endocrine therapy arm on both caliper (chemotherapy 83.9% vs endocrine therapy 71.3%, OR 0.476 95% CI 0.228 to 0.994) and MRI (chemotherapy 83.7% vs endocrine therapy 52.9%, OR 0.219, 95% CI 0.107 to 0.447). Three patient on chemotherapy group (3.4%) and 1 patients (1.15%) on endocrine treatment group showed complete pathologic response. In the patients who had breast cancer with low Ki 67 expression (&lt;20%) on initial biopsy, clinical response on caliper were shown similar on both treatment group (HR 0.958, 95%CI 0.296 to 3.101). Five patients who had no tumor on the breast or lymph node after 24 week neoadjuvant endocrine therapy had higher ER score (all allred score &gt;6), all low grade (1or 2) low Ki 67(≤20%) expression (4/5 patients) on initial biopsy specimen. Conclusions: In premenopausal breast cancer patients, 24 weeks neoadjuvant chemotherapy showed better clinical response than endocrine therapy. Low Ki 67 expression could be a parameter of the endocrine treatment. Clinical trial information: NCT01622361.
Beyond epithelial‐to‐mesenchymal transition: Common suppression of differentiation programs underlies epithelial barrier dysfunction in mild, moderate, and severe asthma
Authors: L. F. Loffredo, H. Abdala‐Valencia, K. R. Anekalla, L. Cuervo‐Pardo, C. J. Gottardi, S. Berdnikovs
Journal: Allergy (2017)

Abstract Background Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial‐to‐mesenchymal transition ( EMT ) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial‐mesenchymal signaling, and their relationship to asthma severity, are poorly understood. Methods We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts. Results We found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB 2, FGFR 1, FGFR 2, INSR , IRS 2, NOTCH 2, TLE 1, and NTRK 2 as novel markers central to dysregulation of epithelial‐mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this “core” signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings. Conclusions The comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de‐differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.
DNA methylation-based chromatin compartments and ChIP-seq profiles reveal transcriptional drivers of prostate carcinogenesis
Authors: Poppy Simmonds, Erick Loomis, Edward Curry
Journal: Genome Medicine (2017)

Profiles of DNA methylation of many tissues relevant in human disease have been obtained from microarrays and are publicly available. These can be used to generate maps of chromatin compartmentalization, demarcating open and closed chromatin across the genome. Additionally, large sets of genome-wide transcription factor binding profiles have been made available thanks to ChIP-seq technology. We have identified genomic regions with altered chromatin compartmentalization in prostate adenocarcinoma tissue relative to normal prostate tissue, using DNA methylation microarray data from The Cancer Genome Atlas. DNA binding profiles from the Encyclopedia of DNA Elements (ENCODE) ChIP-seq studies have been systematically screened to find transcription factors with inferred DNA binding sites located in discordantly open/closed chromatin in malignant tissue (compared with non-cancer control tissue). We have combined this with tests for corresponding up-/downregulation of the transcription factors' putative target genes to obtain an integrated measure of cancer-specific regulatory activity to identify likely transcriptional drivers of prostate cancer. Generally, we find that the degree to which transcription factors preferentially bind regions of chromatin that become more accessible during prostate carcinogenesis is significantly associated to the level of systematic upregulation of their targets, at the level of gene expression. Our approach has yielded 11 transcription factors that show strong cancer-specific transcriptional activation of targets, including the novel candidates KAT2A and TRIM28, alongside established drivers of prostate cancer MYC, ETS1, GABP and YY1. This approach to integrated epigenetic and transcriptional profiling using publicly available data represents a cheap and powerful technique for identifying potential drivers of human disease. In our application to prostate adenocarcinoma data, the fact that well-known drivers are amongst the top candidates suggests that the discovery of novel candidate drivers may unlock pathways to future medicines. Data download instructions and code to reproduce this work are available at GitHub under 'edcurry/PRAD-compartments'.
New AML Therapy and Diagnostic
Authors: Rebecca Voelker
Journal: JAMA (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 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
Tumor-infiltrating lymphocytes as a prognostic factor in patients with stage I to III breast cancer.
Authors: Eduardo Richardet, Luciana Paola Acosta, Martin Paradelo, Martin Pairola, Cecilia Di Tada, Matias Molina, Luciano Salvador Dicalbo, Rocio Paola Villavicencio, Martin Eduardo Richardet
Journal: Journal of Clinical Oncology (2017)

e12042 Background: Current evidence makes reference to the potential role that tumor-infiltrating lymphocytes (TILs) as a prognostic factor in breast cancer and numerous types of tumors. Different studies have shown that the interaction with the immune response of the host is relevant to the response to chemotherapy. TILs are cell phenotype T CD3 +, which can, in turn, stratify in cytotoxic T lymphocytes (CD8), and regulatory T cells (CD4+ CD25+ FOXP3+).Our aim was to identify whether there was a relationship between TILs and SLE in patients with stage I to III breast cancer who have undergone chemotherapy adjuvant treatment. The secondary endpoint was to analyze the association between subtype infiltrating lymphocytes (CD4 and CD8) and SLE. Methods: Retrospective and analytical study in our institution IONC. Patients with stage I to III breast cancer was analized which had standard risk factors and required adjuvant treatment with chemotherapy. 87 patients completed with the selection criteria. The infiltration degree by H/E was evaluated and CD4 and CD8 by IHQ was marked. SLE was analyzed through the Kaplan-Meier method. Results: 87 samples were analyzed, in 46 patients (52,8 %) evidenced TILs and in 41 patients (47.12%) there were no TILs in their tumor samples. SLE was higher for those patients who had TILs with respect to those patients who did not have any TILs, 45.3 months as opposed to 30.85 months respectively (p: 0,038) and these differences were statistically different. In the TILi analysis, it could observed that 91% patients not revealed infiltrations in their tumor samples.When correlating CD4 and CD8 was carried out, 33% of the patients showed CD4 TILs in their tumor samples and 49.4% evidenced CD8 TILs. There were no SLE differences regarding the presence or the absence of CD4. The high number of CD8 was associated to a higher SLE; 39.06 months as opposed to 37.5 months, but these differences were not statistically different. Conclusions: We could conclude that patients who had showed TILs in their tumor samples had a higher SLE with respect to those who did not show any infiltration and this was statistically significant. There were no differences when samples were analyzed on the presence or absence of CD4 and CD8.
Trauma staff change routines in wake of terrorist attack
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Doctors involved in trauma care are changing their usual routines when they are not at work to ensure that they can respond to emergency calls, with some not drinking alcohol on a night off, for example.

Malik Ramadhan is clinical director for emergency care and trauma at the Royal London Hospital in Whitechapel, which treated 12 of the 48 injured people taken to hospital after Saturday’s terrorist attack on London Bridge and in the adjacent Borough area. He told the BBC Radio 4 Today news programme on 5 June that the major trauma system in London had been preparing itself for some time for the sorts of incidents that hospital emergency teams had faced in recent weeks.

Doctors were making sure that they were able to respond even when they were not officially on call, he said. “Doctors like myself who might have been going to Borough [for a few drinks] after a night at work [are not],” he said. “As Saturday night is testament, we had a lot of people who were completely sober and willing …
Preliminary Results of the Flugaza Trial: A Phase III Randomized, Open Label Study Comparing Azacytidine Versus Fludarabine and Cytarabine (FLUGA Scheme) in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia
Authors: Pau Montesinos, Susana Vives, Maria P Martinez-Sanchez, Juan Bergua, Lorenzo Algarra, Herrera Pilar, Mar Tormo, Jose-Luis Lopez-Lorenzo, Fernando Ramos, Jose Francisco Falantes, Olga Salamero, Josefina Serrano, Cristina Gil, Maria L Amador, Esperanza Lavilla, Maria J Sayas, Maria Teresa Olave, Belen Vidriales, David Martínez-Cuadrón, Miguel Ángel Sanz
Journal: Blood (2016)
Aspirin to inhibit the formation and EMT of circulating tumor cells in patients with metastatic colorectal cancer but not breast cancer.
Authors: Chao Ni, Liu Yang
Journal: Journal of Clinical Oncology (2017)

e23024 Background: High circulating tumor cells (CTCS) have been acknowledged as a poor indication in malignant disease. Besides, platelets are found play crucial role in tumor cells’ epithelial – mesenchymal transition and metastasis, so here we test if disruption of platelet function with aspirin, could decrease the number and inhibit the EMT of CTCs in metastatic colorectal (MCC) or breast cancer (MBC). Methods: Patients with MCC or MBC who were not receiving cytotoxic chemotherapy currently (except for capecitabine maintenance), while endocrine therapy, bisphosphonate or molecular targeted therapy were accepted. Base line of Platelet aggregation rate (PAR), CTCs’ number and molecular phenotype were recorded. Patients whose CTCs ≥ 5 cells/7.5ml peripheral blood were included and receive aspirin 100mg/day for the following 8 weeks. Then the phlebotomy was performed at 4, 8 weeks thereafter to obtain specimen and assess PAR, CTCs’ number and phenotype. The phenotypes of CTCs were classified into epithelial (E+), mesenchymal(M+) and middle type(express both E+ and M+ markers) with fluorescence in situ hybridization assay. Results: Forty patients (19 MBC and 21 MCC patients ) were enrolled. Base line CTC numbers were 8.7± 3.4 in MBC patients, the ratio of E+ and M+ type were 48.2 ± 22.4% and 25.1 ± 14.9% respectively; the base line CTC numbers were 10.7 ± 4.8 in MCC patients, and the ratio of E+ and M+ type were 45.3 ± 27.3% and 22.0 ± 18.5% respectively. Despite adequate platelets inhibition in both groups, CTC numbers were similar in MBC patients in the following 8 weeks ( p= 0.0532 ), while the fraction of E+ or M+ CTCs were also unchanged (E+ CTCs p= 0.305; M+ CTCs p= 0.09); however, both CTC numbers and fraction of M+CTCs were markedly decreased in MCC patients (total numbers: p&lt; 0.01; E+ CTCs p= 0.031; M+ CTCs p= 0.013) . Conclusions: Aspirin could decreased the number of CTCs and block EMT transition in MCC patients, and our results provide potential explanation of how aspirin impede the metastasis of colorectal cancer. But this effect could not be observed in MBC patients. Future studies evaluating the underlying mechanism of this differences remain of interest, and they may be informed by our results. Clinical trial information: NCT02602938.