tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx
Authors: Ankur Chakravarthy, Stephen Henderson, Stephen M. Thirdborough, Christian H. Ottensmeier, Xiaoping Su, Matt Lechner, Andrew Feber, Gareth J. Thomas, Tim R. Fenton
Journal: Journal of Clinical Oncology (2016)

Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors. Methods Meta-analysis was used to build a cross-tissue gene-expression signature for HPV-driven cancer. Classifiers trained by machine-learning approaches were used to predict the HPV status of 520 HNSCCs profiled by The Cancer Genome Atlas project. DNA methylation data were similarly used to classify 464 HNSCCs and these analyses were integrated with genomic, histopathology, and survival data to permit a comprehensive comparison of HPV transcript-positive OPSCC and non-OPSCC. Results HPV-driven tumors accounted for 4.1% of non-OPSCCs. Regardless of anatomic site, HPV+ HNSCCs shared highly similar gene expression and DNA methylation profiles; nonkeratinizing, basaloid histopathological features; and lack of TP53 or CDKN2A alterations. Improved overall survival, however, was largely restricted to HPV-driven OPSCCs, which were associated with increased levels of tumor-infiltrating lymphocytes compared with HPV-driven non-OPSCCs. Conclusion Our analysis identified a causal role for HPV in transcript-positive non-OPSCCs throughout the head and neck. Notably, however, HPV-driven non-OPSCCs display a distinct immune microenvironment and clinical behavior compared with HPV-driven OPSCCs.
Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice
Authors: Annika Reinhardt, Tetyana Yevsa, Tim Worbs, Stefan Lienenklaus, Inga Sandrock, Linda Oberdörfer, Thomas Korn, Siegfried Weiss, Reinhold Förster, Immo Prinz
Journal: Arthritis & Rheumatology (2016)

Objective The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin‐23 (IL‐23) is involved in the pathogenesis of SpA by acting on IL‐23 receptor (IL‐23R) expressed on enthesis‐resident lymphocytes. Upon IL‐23 binding, CD3+CD4−CD8− tissue‐resident lymphocytes secrete IL‐17A and IL‐22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis‐resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis. Methods We used 2‐photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd‐H2BeGFP , Rorc‐GFP , and IL‐23R‐eGFP mice. To analyze entheseal γ/δ T cells in IL‐23−induced inflammation, Tcrd‐H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL‐23 minicircle DNA was performed for overexpression of IL‐23 and induction of inflammation. Light‐sheet fluorescence microscopy was used to visualize arthritic inflammation. Results Activated Vγ6+CD27− γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor−related orphan nuclear receptor γt (RORγt)+IL‐23R+ enthesis‐resident lymphocytes. Fetal thymus−dependent γ/δ T cells were the main source of IL‐17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body. Conclusion Entheseal γ/δ T cells are derived from fetal thymus and are maintained as self‐renewing tissue‐resident cells. As main IL‐17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL‐23−induced local inflammation.
What’s in<i>Your</i>Library?
Authors: Jack Coulehan
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
Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters
Authors: Anders Carlsson, Peter Kuhn, Madelyn S. Luttgen, Kevin Keomanee-Dizon, Patricia Troncoso, Paul G. Corn, Anand Kolatkar, James B. Hicks, Christopher J. Logothetis, Amado J. Zurita
Journal: Clinical Cancer Research (2016)

Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information.
Randomized trial of yoga in women with breast cancer undergoing radiation treatment: Long-term effects
Authors: L. Cohen, K. D. Chandwani, G. Perkins, B. Thornton, B. Arun, N. V. Raghuram, H. R. Nagendra
Journal: Journal of Clinical Oncology (2008)

9639 Background: A yoga program was developed that included postures, a breathing exercise, a relaxation technique, and meditation for patients with breast cancer who were undergoing radiotherapy. We previously reported on the short-term benefits of yoga at improving physical functioning and general health perceptions at the end of radiotherapy. Methods: Women participated in bi-weekly classes during their 6 weeks of radiation treatment. Sixty-one women with breast cancer were randomly assigned to either the yoga program or to a waitlist control group. Patients completed measures of intrusive thoughts (Impact of Events Scale: IES), depressive symptoms (CES-D), sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (BFI), quality of life (SF-36), and Finding Meaning in Cancer (FM) at baseline, 1 week, and 1 and 3 months after the last radiation therapy. We report on the outcomes 1 and 3 months after the end of radiotherapy. Results: The average age was 52, 3% stage 0, 28% stage I, 43% stage II, and 26% stage III, 48% had undergone breast-conserving surgery, and 75% had received chemotherapy. Analysis of covariance, controlling for baseline, age, stage of cancer, time since diagnosis, type of surgery, and prior chemotherapy (yes/no) revealed that the yoga group had significantly higher IES scores 1 month after radiotherapy (adjusted means: yoga 7.1 vs. control 4.1, P=0.01) and significantly higher FM scores 3 months after radiotherapy (adjusted means: yoga 52.8 vs. control 47.3, P=0.01). There were no other group differences on any scales. Interestingly, there was a positive correlation between IES scores at 1 month and FM scores at 3 months (P=0.02) suggesting that the more intrusive thoughts at 1 month the greater the finding meaning at 3 months. Regression analyses including group and IES scores at 1 month in predicting FM scores at 3 months revealed that IES scores remained a significant predictor in the model and group was no longer significant, suggesting that intrusive thoughts mediated the effects of group on FM scores. Conclusions: The results indicated that the yoga program was associated with increased finding meaning in the cancer experience 3 months after the end of radiotherapy and that this was mediated through increases in intrusive thoughts at 1 month. No significant financial relationships to disclose.
Amphotericin B colloid dispersion (ABCD) for the treatment of proven or presumed fungal infections in immunocompromised patients with hematologic malignancies
Authors: B Sirohi, R Powles, J Treleaven, S Singhal, S Kulkarni, R Saso, CR Pinkerton, S Meller, S Vaidya, K Murphy, A Conway, C Seybel, D Cunningham, J Mehta
Journal: Blood (2000)
Reply to Che-Kai Tsao, Matthew D. Galsky, and William K. Oh's Platinum Opinion. Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer: Urgent Need To Minimize The Risk Of Neutropenic Fever. Eur Urol 2016;70:707–708
Authors: Matthew R. Sydes, Alastair W.S. Ritchie, Nicholas D. James
Journal: European Urology (2016)
Clinical features of gefitinib-responders with non-small cell lung cancer
Authors: M. Shenglin, X. Yaping, D. Qinghua, Y. Xinmin
Journal: Journal of Clinical Oncology (2008)

19136 Background: Although chemotherapy improves survival in advanced NSCLC patients, it appears to have reached a therapeutic plateau and novel approaches are urgently required. Under these circumstances, inhibition of the epidermal growth factor receptor (EGFR) tyrosine kinase has emerged as a therapeutic option in patients with NSCLC. Gefitinib, an oral EGFR tyrosine kinase inhibitor (EGFR- TKI), is a leading agent in this class of novel therapeutic agents. Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we reviewed the outcomes of gefitinib-responders treated with gefitinib at our institution. Patients and Methods: We retrospectively evaluated the clinical courses of 31 NSCLC patients between October 2004 and June 2007 who received 250 mg/day gefitinib orally and achieved either a complete or partial response. These patients form the basis of this study. There were 17 women and 14 men. There were 13, 3 and 15 patients with cigarettes-year ≥400, cigarettes-year<400 and never a smoker, respectively. Results: At 6 months, patients who achieved either a complete or partial response all were adenocarcinoma. Favorable efficacy was observed in the primary lesion and metastases to the lung, pleura, peritoneum, pericardium, liver, brain and bone. The brain metastasis was the site of major recurrence. Median period for a patient to have improved symptoms was 15 days. Median progression-free survival (PFS) was 10.0 months, median duration of gefitinib treatment was 13.0 months. Gender and smoking status were not correlated to PFS. Rash and diarrhea were the most common adverse events, which were manageable and reversible. None of patients was withdrawn due to the adverse events. Conclusion: Patients of Asian origin with advanced lung adenocarcinoma patients who were refractory to or intolerant of their most recent chemotherapy regimen, gefitinib at a dosage of 250 mg/day was effective. Gender and smoking status were not correlated to PFS. The results of this study should help to further identify which patients are most likely to benefit from treatment with gefitinib. No significant financial relationships to disclose.
Non-communicable diseases now cause two thirds of deaths worldwide
Authors: Susan Mayor
Journal: BMJ (2016)

Average life expectancy across the world has increased by more than 10 years since 1980, but non-communicable diseases now account for more than two thirds of all deaths, a new analysis of global health data has shown.1

The Global Burden of Disease Study 2015 analysed the latest available data for 249 causes of death, 315 diseases and injuries, and 79 risk factors in 195 countries and territories from 1990 to 2015. Researchers estimated all cause mortality by age, sex, geography, and year using what they said was a more accurate approach than previous methods, with better estimates …
TLE3 as a biomarker for taxane sensitivity in breast cancer
Authors: S. Kulkarni, D. G. Hicks, N. Watroba, C. Murekeyisoni, R. Beck, B. Z. Ring, N. Estopinal, M. T. Schreeder, R. S. Seitz, D. T. Ross
Journal: Journal of Clinical Oncology (2008)

573 Background: The addition of taxanes (T) to chemotherapeutic regimens has not demonstrated a consistent therapeutic benefit in early stage breast cancer (Ward, HTA 2007). A recent study by Hayes, et al. suggested that HER2+ breast tumors may gain increased clinical benefit from treatment with T. The toxicity associated with T therapy compels a search for additional and or refined biomarkers of response. Methods: A dataset of IHC stains in 411 patients from Clearview Cancer Center (CCI) was mined to identify biomarkers of T response (Ring, JCO 2006). TLE3 staining with a polyclonal antibody was nominated as a candidate T-response predictor. The association with T sensitivity was tested by staining with anti-TLE3 antibody on an independent triple-negative (TN) validation cohort assembled at the Roswell Park Cancer Institute (RPCI). Results: TLE3 was identified as a candidate T sensitivity marker in the CCI cohort by identifying patients with improved five-year disease-free interval (DFI) in overall cohort (n=441, p<0.004), patients treated with CMF (n=72 p<0.02), or those treated with a AC+T regimen (n=65 p<0.04) but no association of staining with outcome in untreated patients (n=203 p=0.49) or those treated with a AC without T (n=66 p=0.97). In the RPCI TN validation cohort, TLE3 staining was significantly associated with improved five-year DFI in T treated patients (n=45 p<0.02) and all patients (n=81 p<0.015) but not AC treated patients (n=17 p=0.81). These associations were independent of grade, tumor size and nodal status in both cohorts. Conclusions: TLE3 staining is associated with improved DFI in taxane-treated patients in two independent cohorts. Given that the validation cohort was triple negative, it is unlikely that TLE3 is serving as a surrogate for ER or HER2 expression. TLE3 should be studied in large clinical trial cohorts to establish its role in taxane chemotherapy selection. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Applied Genomics Applied Genomics Applied Genomics Applied Genomics
Long Term Results from the Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO-I) Trial: Sustained Benefit of Fibrin-Specific Therapy
Authors: BE Tardiff, B McCants, AS Hellkamp, KL Lee, DB Mark, Frans Van de Werf, ER Bates, R Carliff
Journal: Circulation (1999)
Case series of EGFR C797S mutations in non-small cell lung cancer identified with cell-free circulating tumor DNA next generation sequencing.
Authors: Stephen R Fairclough, Oliver A. Zill, Darya Chudova, Christine Elaine Lee, Richard Burnham Lanman, Kimberly C. Banks, Rebecca J Nagy, Stefanie Mortimer, Helmy Eltoukhy, AmirAli Talasaz, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2016)

e23021 Background: In non-small cell lung cancer (NSCLC), targeted treatment with first line tyrosine kinase inhibitors (TKIs) selects for the evolution of resistance at EGFR T790M in 50% of cases. To address this clinical challenge, third-generation pyrimidine-based EGFR TKIs with selectivity for EGFR T790M over wild-type EGFR have been developed. These drugs form a covalent bond with cysteine 797 in the adenosine triphosphate–binding pocket. Here we report a case series of EGFR C797S mutations identified with cell-free circulating tumor DNA (cfDNA) next generation sequencing (NGS). Methods: Guardant360 utilizes cfDNA NGS to target 70 genes for single nucleotide variants (SNVs), including all 28 exons and partial introns in EGFR. EGFR C797S SNVs were identified in the Guardant Health database of 13,987 cfDNA samples (12,086 patients) from June 2014 through January 2016 and phased with the neighboring T790M mutation to determine if these mutations occurred in cis or trans. Results: T790M mutation was identified in 311 NSCLC patients (352 samples) and 8 of whom had C797S mutations (11 samples). EGFR exon 19 deletions were the primary EGFR driver, with a median mutant allele fraction (MAF) of 6.55% (range 0.4% to 64.1%). T790M mutations in samples with C797S mutations had a median MAF of 1.42% (range 0.58% to 37.61%). C797S mutations were observed in cis with T790M in 8 cases and had an initial median MAF of 0.33% (range 0.14% to 33.01%), which composed 12%-100% (median 45.21%) of the T790M fraction. Five patients with C797S mutations had samples collected prior to the emergence of T790M. The average time from T790M detection to C797S detection was 77 days. Five patients’ tumors evolved two simultaneous C797S mutations, consistent with convergent sub-clonal evolution after third generation TKI treatment. Conclusions: The detection of drug resistance mutations in NSCLC patients with cfDNA NGS demonstrates that cfDNA NGS can identify and quantify resistance mutations that arise under selective treatment pressure without the need for invasive biopsy and assist clinicians in determining the timing and selection of next line therapy.
SWOG S1404: A phase III randomized trial comparing standard of care adjuvant therapy to pembrolizumab in patients with high risk resected melanoma.
Authors: Kenneth F. Grossmann, Megan Othus, Ahmad A. Tarhini, Sapna Pradyuman Patel, James Moon, Vernon K. Sondak, John M. Kirkwood, Antoni Ribas
Journal: Journal of Clinical Oncology (2016)

e21032 Background: With the recent FDA approval of ipilimumab, the treatment options available to patients with high risk resected melanoma has changed. Now, reasonable treatment choices include high dose interferon, ipilimumab dosed at 10 mg/kg, and pegylated interferon. Among these treatments, HDI remains the only treatment to show an overall survival benefit in randomized trials. With the high response rates, and relatively low toxicity profile seen in the treatment of Stage IV melanoma with pembrolizumab, investigation of this agent in stage III patients is a critical priority. S1404 is a randomized trial comparing standard of care HDI to pembrolizumab in patients at high risk for recurrence and death after surgery. Methods: Patients age 18 or greater with Stages IIIA(N2), IIIB, IIIC and IV (M1a, b and c) are eligible. Patients with brain metastasis will be excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel lymph node positive disease. Prior therapy with PD-1 blockade or interferon are not allowed. Two treatment arms are assigned based on stratification by stage and PD-L1 staining status (positive vs negative vs unknown). Patients (n = 1,378) will be randomized 1:1 to either 1) interferon Alfa-2b 20 MU/m2/days 1-5 weeks 1-4, followed by Interferon Alfa-2b 10 MU/m2/d SC days 1,3,5weeks 5 -52, or 2) pembrolizumab 200 mg day 1, q 3 weeks for 52 weeks. Efficacy will be measured in terms of both overall survival and relapse free survival, with interim analyses planned for both endpoints at 50% OS information. Safety, pharmacokinetics, and quality of life data will also be studied. Results: As of January 29, 2016, 36 sites are registered, 29 patients are in screening, and 13 patients randomized. An amendment to include 10 mg/kg ipilimumab as a treatment option is under review and will be described at the annual meeting. Conclusions: Support: NIH/NCI NCTN grants CA180888, CA180819, CA180818, CA180826, CA180858, CA180820, CA180844 Clinical trial information: MCT02506153.
Intrafistular Injection of AUTOLOGOUS BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS for the TREATMENT of Refractory Perianal CROHN'S DISEASE.
Authors: Maria Ester Bernardo, Rachele Ciccocioppo, Maria Antonietta Avanzini, Adele Sgarella, Maria Luisa Russo, Cristina Ubezio, Federico Bonetti, Mara Scabini, Costanza Alvisi, Ombretta Luinetti, Cesare Perotti, Rita Maccario, Laura Salvaneschi, Fabrizio Calliada, Paolo Dionigi, Gino Roberto Corazza, Franco Locatelli
Journal: Blood (2009)
Defibrotide Low-Dose Continuous Infusion After Allogeneic Stem Cell Transplantation as Prophylaxis for Veno-Occlusive Disease of the Liver.
Authors: Alessandro Bonini, Annalisa Imovilli, Angelo Ghirarduzzi, Mauro Silingardi, Annalisa Pilia, Luigi Gugliotta, Francesco Merli
Journal: Blood (2010)
Constitutive Activation of the Canonical NF-κB Signaling Pathway and Expanded Populations of Splenic Marginal Zone B Cells Characterize Em-BCL10 Transgenic Mice.
Authors: Zhaoyang Li, Liquan Xue, Dong-Mi Shin, Chen-Feng Qi, Quangeng Zhang, Wu Xu, Stephan W. Morris, Herbert Morse, Hongsheng Wang
Journal: Blood (2007)
P2.47 (also presented as PD1.02): The Role of PD-L1 Expression as a Predictive Biomarker in Advanced NSCLC: An Update of a Network Meta-Analysis
Authors: Pedro Aguiar, Gilberto Lopes, Ilka Santoro, Hakaru Tadokoro, Carmelia Barreto, Ramon De Mello
Journal: Journal of Thoracic Oncology (2016)