tbuckley/cabot-search huggingface dataset:
Nobel Laureates Pick Food Fight With GMO Foes
Authors: Jeff Lyon
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
P1019 : The impact of metabolic syndrome on ALT levels among the large multiethnic cohort of North American patients with chronic hepatitis B infection enrolled in the Hepatitis B Research Network (HBRN)
Authors: M. Khalili, M. Lombardero, J. Feld, M. Shuhart, R. Chung, N. Terrault, K. Kowdley, M. Lisker-Melman, M. Ghany, W.R. Kim, A. Sanyal, A. Lok
Journal: Journal of Hepatology (2015)
Genomic Approaches to Understanding Response and Resistance to Immunotherapy
Authors: David A. Braun, Kelly P. Burke, Eliezer M. Van Allen
Journal: Clinical Cancer Research (2016)

Abstract Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for patients with advanced cancers. However, such therapy has benefited only a subset of patients, with some patients failing to respond to treatment at all and others achieving a limited response followed by tumor progression. Understanding factors contributing to an effective response and further elucidating mechanisms of resistance will be crucial as these therapies are applied more broadly. Genomics-based approaches have significantly advanced the study of response and resistance to immunotherapy in general, and to immune checkpoint blockade more specifically. Here, we review how genomic and transcriptomic approaches have identified both somatic and germline positive correlates of response, including high mutational/neoantigen load and low intratumoral heterogeneity, among others. The genomic analysis of resistant tumors has additionally identified crucial factors involved in resistance to immune checkpoint blockade, including loss of PTEN and upregulation of other immune checkpoints. Overall, the continued use of genomic techniques at the point of care, combined with appropriate functional studies, would ideally lead to a better understanding of why certain patients respond to immune-based therapies, allowing clinicians to identify the subset of patients likely to benefit from such therapy, and potentially providing insight into how other therapies may be added in combination to increase the number of patients who may benefit from immunotherapy. Clin Cancer Res; 22(23); 5642–50. ©2016 AACR.
Combined blockade of the IL-13 and IL-33 pathways leads to a greater inhibition of type 2 inflammation over inhibition of either pathway alone
Authors: Vladimir Ramirez-Carrozzi, Arivazhagan Sambandam, Meijuan Zhou, Donghong Yan, Jing Kang, Xiumin Wu, Eric Suto, Miriam Baca, Cary Austin, Min Xu, Wyne Lee, Rajita Pappu
Journal: Journal of Allergy and Clinical Immunology (2016)
<i>Notes from the Field</i>: Measles Outbreak of Unknown Source — Shelby County, Tennessee, April–May 2016
Authors: Mary-Margaret A. Fill, David Sweat, Helen Morrow, Alisa Haushalter, Judy C. Martin, Tyler Zerwekh, Tamal Chakraverty, Jennifer Kmet, Kevin Morris, Kelly Moore, Marion Kainer, Rendi Murphree, John R. Dunn, William Schaffner, Timothy F. Jones
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On April 15, 2016, local public health officials in Shelby County, Tennessee, were notified of a positive measles immunoglobulin M (IgM) test for a male aged 18 months (patient A). On April 18, 2016, a second positive measles IgM test was reported for a man aged 50 years (patient B). Both patients had rash onset on April 9, 2016. The Shelby County Health Department initiated an investigation, and confirmatory testing for measles virus on oropharyngeal swabs by polymerase chain reaction (PCR) at CDC was positive for both patients. On April 21, 2016, public health officials were notified of a third suspected measles case in a female aged 7 months (patient C) who had developed a rash on April 14; PCR testing was positive. Genotyping conducted at CDC identified genotype B3 measles virus in all three cases. Genotype B3 is known to be circulating globally and has previously been associated with imported cases in the United States (1).
Taurine-Conjugated Bile Acids Protect Expanding Hematopoietic Stem/Progenitor Cells from Unfolded Protein Stress As Natural Chaperones
Authors: Valgardur Sigurdsson, Hajime Takei, Svetlana Soboleva, Takashi Iida, Hiroshi Nittono, Kenichi Miharada
Journal: Blood (2014)
Response by Wirtz et al to Letter Regarding Article, “Access to Medications for Cardiovascular Diseases in Low- and Middle-Income Countries”
Authors: Veronika J. Wirtz, Warren A. Kaplan, Gene F. Kwan, Richard O. Laing
Journal: Circulation (2016)

In Response:We greatly appreciate the positive comments regarding our article 1 in the letter from Antignac et al.We agree that there is a dearth of published information about the quality of noncommunicable disease medicines including cardiovascular.In 2011, contamination of a cardiovascular medicine in Lahore, Pakistan, caused nearly 200 deaths among up to 40 000 exposed patients. 2,3This major incident led to the establishment of the Judicial Inquiry Tribunal to determine the causes of patient deaths in Lahore in 2011 and 2012. 4 Investigating and implementing corrective actions is 1 way of preventing other similar incidents.Agreeing on a standard terminology and understanding the extent of the problem are 2 other areas where urgent global and national action is required.The Institute of Medicine published a comprehensive report on this topic titled "Countering the Problem of Falsified and Substandard Drugs." 5 The report standardizes the terms describing the different mechanisms resulting in poor-quality medicines:1. Counterfeit: the unauthorized use of a trademark to identify a medicine.2. Falsified: a medicine in which there is an intention to deceive.3. Substandard: a product that fails to meet pharmacopeial standards.4. Unregistered: product that lacks market authorization from the national regulatory authorities.The standard definitions are important because the national and international response will vary according to which problem is faced.A short section in the Institute of Medicine report indicates that problems of medicine quality exist for different types of noncommunicable diseases.However, assessing the prevalence of poor-quality noncommunicable disease medicines and the resulting health and economic implications is not possible because of the lack of data.Last, apart from regulatory authorities, wholesalers and procurement agencies play an important role in promoting quality-assured medicine by testing the quality of medicines they sell or procure. 6n summary, effective regulation and active quality surveillance mitigate the risk of harm to patients.In countries where regulatory bodies are unable to ensure the quality of circulating products, procurement organizations must ensure that they are of adequate quality and that they test the products before they sell them.
Second generation antihistamines after breast cancer diagnosis to improve prognosis both in patients with ER+ and ER- breast cancer.
Authors: Hakan Lars Olsson, Rickard Einefors, Per Broberg
Journal: Journal of Clinical Oncology (2015)

3062 Background: Subgroups of patients with breast cancer (BC) could be candidates for immunological interventions. In the present investigation the role of antihistamines on prognosis of breast cancer has been studied, especially comparing first and second generation H-1 receptor antagonists due to their possible different effects on cytokines. Methods: The study includes all women with BC diagnosed in Sweden 2000 through 2008 (n = 54406). Dates of birth, BC diagnosis and TNM-stage were directly extracted from the cancer registry. Therapy with antihistamines was gathered from the Swedish Prescription Registry. Other registries utilised were the Cause of Death Registry, Population Registry, and the in patient or out patient registries. BC and overall survival was compared between users of antihistamines and non users. Analyses were adjusted for TNM-stage, receptor status and age at diagnosis. A late entry model was used for different types of antihistamines. Results: The HR for BC specific survival for the combined group of antihistamine users (n = 9777) was 0.70 (0.66-0.75). All the effect was seen for use after BC diagnosis. Results remained after adjusting for out or in patient diagnoses of allergy. In late entry models women using desloratadine (n = 1895) had a HR of 0.69 (0.52-0.91). Loratadine users (n = 2132) HR of 0.74 (0.60-0.93). Cetirizine users (n = 3001) HR of 1.13 (0.96-1.33) and Klemastine users (n = 2278) had a HR of 0.98 (0.80-1.19). Ebastin users (n = 326) had a HR of 0.50 (0.22-1.12) and Fenofexadine users (n = 145) had a HR of 0.73 (0.30–1.76). The analyses was also stratified for ER-status, but the results did not differ noticeably. Results were similar when overall survival was analysed. Conclusions: This population based registry study shows that women treated with second generation antihistamines have a better overall and BC specific survival compared with non users regardless of age, history of allergy, ER status and tumor stage. The results are strongest for desloratadine use and use after BC diagnosis. Second generation antihistamines could offer a nontoxic therapy for both receptor positive and negative BC. The mechanism behind this effect is presently unknown.
Ovarian Cancers Harbor Defects in Nonhomologous End Joining Resulting in Resistance to Rucaparib
Authors: Aiste McCormick, Peter Donoghue, Michelle Dixon, Richard O'Sullivan, Rachel L. O'Donnell, James Murray, Angelika Kaufmann, Nicola J. Curtin, Richard J. Edmondson
Journal: Clinical Cancer Research (2016)

DNA damage defects are common in ovarian cancer and can be used to stratify treatment. Although most work has focused on homologous recombination (HR), DNA double-strand breaks are repaired primarily by nonhomologous end joining (NHEJ). Defects in NHEJ have been shown to contribute to genomic instability and have been associated with the development of chemoresistance.
Clinical pattern and implication of PD-L1 expression in soft-tissue sarcoma.
Authors: Chan Kim, Eun Kyung Kim, Jung Woo Han, Hong Jae Chon, Su Jin Heo, Young Han Lee, Yong Jin Cho, Jin-Suck Suh, Kyoo-Ho Shin, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha, Soo Hee Kim, Hyo Song Kim
Journal: Journal of Clinical Oncology (2015)

10565 Background: PD-1/PD-L1 axis plays a paramount role in tumor immune escape by negative regulation of T-cell functions. Recently, immune checkpoint inhibitors targeting this axis displayed promising anti-tumor activity with durable response, and the predictive role of PD-L1 expression is being investigated in various solid tumors. In the present study, we aimed to characterize the PD-L1 expression pattern and its clinical implication in soft-tissue sarcomas (STS). Methods: We analyzed PD-L1 expression in 82 STS patients with 5 subtypes including rhabdomyosarcoma (n = 32), synovial sarcoma (n = 19), Ewing sarcoma (n = 18), epithelioid sarcoma (n = 7), and mesenchymal chondromsarcoma (n = 6). PD-L1 expression was evaluated using anti-PD-L1 antibody (clone 130021, R&D System), and PD-L1 positivity was defined as more than 10% of PD-L1 staining in tumor cells. PD-L1 expression was compared with other clinicopathologic variables. Results: Median age at diagnosis of patient cohort was 26 (range: 1-78) and male-to-female ratio was 1.6. Initial disease presentation was locoregional disease in 80% of patients and metastatic disease in the remaining 20%. PD-L1 expression was identified in 43% of STS patients. Histologic subtype of STS was significantly associated with PD-L1 expression (p = 0.004). Proportion of PD-L1 expressing tumors was highest in epithelioid sarcoma (100%, 7/7), followed by synovial sarcoma (53%, 10/19), rhabdomyosarcoma (38%, 12/32), and Ewing sarcoma (33%, 6/18), while it was not expressed in mesenchymal chondrosarcoma (0%, 0/6). Baseline clinical characteristics other than histologic subtype was not correlated with PD-L1 expression. Patients with PD-L1 expression had worse overall survival compared with those without PD-L1 expression (5-year survival rate: 48% in PD-L1 positive vs. 68% in PD-L1 negative, p = 0.015). Moreover, this negative prognostic role of PD-L1 expression in STS was also confirmed by multivariate analysis with Cox regression model (HR: 2.67, p = 0.017). Conclusions: PD-L1 is not only expressed in STS but also stand as an independent negative prognostic factor for overall survival of STS patients. Thus, PD-L1 needs to be pursued as a potential therapeutic target in patients with STS.
Tumor macrophages are pivotal constructors of tumor collagenous matrix
Authors: Ran Afik, Ehud Zigmond, Milena Vugman, Mordehay Klepfish, Elee Shimshoni, Metsada Pasmanik-Chor, Anjana Shenoy, Elad Bassat, Zamir Halpern, Tamar Geiger, Irit Sagi, Chen Varol
Journal: The Journal of Experimental Medicine (2016)

Tumor-associated macrophages (TAMs) promote tumor development, invasion, and dissemination by various mechanisms. In this study, using an orthotopic colorectal cancer (CRC) model, we found that monocyte-derived TAMs advance tumor development by the remodeling of its extracellular matrix (ECM) composition and structure. Unbiased transcriptomic and proteomic analyses of (a) TAM-abundant and -deficient tumor tissues and (b) sorted tumor-associated and -resident colonic macrophage subpopulations defined a distinct TAM-induced ECM molecular signature composed of an ensemble of matricellular proteins and remodeling enzymes they provide to the tumor microenvironment. Remarkably, many of these ECM proteins are specifically increased in human CRC versus healthy colon. Specifically, we demonstrate that although differentiating into TAMs, monocytes up-regulate matrix-remodeling programs associated with the synthesis and assembly of collagenous ECM, specifically collagen types I, VI, and XIV. This finding was further established by advanced imaging showing that TAMs instruct the deposition, cross-linking, and linearization of collagen fibers during tumor development, especially at areas of tumor invasiveness. Finally, we show that cancer-associated fibroblasts are significantly outnumbered by TAMs in this model and that their expression of collagen XIV and I is reduced by TAM deficiency. Here, we outline a novel TAM protumoral function associated with building of the collagenous ECM niche.
Colorectal adenocarcinoma in eastern Nigeria: Sub-site distribution and surgical treatment patterns.
Authors: S. N. Anyanwu
Journal: Journal of Clinical Oncology (2010)

e14111 Background: Recent reports indicate that the incidence of colorectal cancer in hitherto low incidence areas is increasing, and with a proportionate shift towards the right colon. Cancer in Nigeria commonly presents late when curative surgery may no longer be feasible driving the generally illiterate patients to alternative care with disastrous consequences. We initiated a prospective study on the sub-site anatomic distribution of colorectal malignancies and the surgical management offered. Methods: All patients with colorectal malignancy seen by the authors at Nnamdi Azikiwe University Teaching Hospital, Nnewi were recruited into the study. The clinical features, sub-site analysis and surgical treatment patterns were assessed. Excluded were malignancies primarily arising from the anus or primarily from non-large gut but with large gut involvement. Results: During the period January 1997 to December 2006 143 cases were seen, with 73 males and 70 females. The ages ranged from 18 to 95 years with a mean of 55.1 (SD 13.75). There was no significant difference in age of occurrence of colonic and rectal carcinoma and in male and female cancer.Colonic carcinoma was proportionately commoner in females while rectal carcinoma was commoner in males. Sixty nine percent of all lesions (74% in males, 63% in females) occurred in the rectum followed by caecum and sigmoid colon with about 13% and 11% respectively. Resection for cure was possible in 45% of all cases (87% for colonic and 26% for rectal lesions) and palliative diversion in 15% (all rectal lesions) A third of all patients (all with rectal neoplasms) declined surgery after the need for permanent colostomy was explained to them. There was no difference in acceptance of surgical treatment in public and private establishments. Conclusions: Colorectal cancer still more commonly affects the rectum the examination of which is within the expertise of the average doctor. In the absence of screening procedures in the foreseeable future public enlightenment to patients and physician continuing education are key to earlier diagnosis when less mutilative procedures acceptable to patients might increase the proportion of patients accepting curative surgery. No significant financial relationships to disclose.
Enhancing enrollment using cohort surveillance for phase II biomarkers driven studies in patients with gastric/GEJ and pancreatic cancer.
Authors: Khaldoun Almhanna, Daniel Sullivan, Melissa Mitchell, Gregory M. Springett, Thea Kalebic, Tim Wyant, Hadi Danaee, William L. Trepicchio, Helen Jump, David Daniels, Shawn Brass, Maria Urdialis, Kyle Hawkins, Shane Huntsman, William S. Dalton
Journal: Journal of Clinical Oncology (2015)

e15017 Background: Molecular-based pt assessment is commonly used to identify proper candidates for targeted therapies. The objective of our investigation was to examine the utility of the Total Cancer Care Protocol (TCC) developed at Moffitt Cancer Center and M2Gen to enhance enrollment into clinical trials which evaluate MLN0264, a novel antibody drug conjugate (ADC). MLN0264 is a first in class ADC targeting Guanylyl cyclase C (GCC). GCC is expressed in approximately 60-70% of GI malignancies. Clinical studies of MLN0264, C26002 and C26003 are conducted in pts with pancreatic and gastric/GEJ cancer which express GCC. TCC is an IRB approved observational study that has enrolled over 110,000 pts since 2006. The protocol prospectively asks for pts’ consent to collect longitudinal clinical data, collect and study biospecimens and the ability to re-contact the pt. Methods: Starting March 2014, TCC consented pts seen in GI clinic with stage I-IV gastric/GEJ and pancreatic cancer were considered for pre-screening. Pts who were not consented were approached as well. Archived tissues were submitted for GCC testing. GCC positive pts were followed. Upon progression of disease, and when appropriate, treating physician discussed enrollment in the phase II study. Studies were opened to accrual in August 2014. Results: Between May 2014 and January 2015, M2Gen sent 261 samples for IHC staining for GCC. 242 samples were considered adequate for testing. 196 pts were characterized as GCC+ based on the current clinical trial criteria. Pts were followed prospectively for disease progression. As a direct result of Cohort Surveillance and within the first 160 days of enrollment, Moffitt treated 20 pts (13 gastric/GEJ and 7 pancreas) with MLN0264. That is significantly higher than other participating large institutions in the United States. Accrual is still ongoing. Conclusions: Using a prospective cohort surveillance approach employed by the TCC for clinical trials enrichment is feasible and effective. It offers a highly efficient approach to enrollment of molecularly-defined subset of pts which is of particular interest in rare and aggressive cancers.
Evaluation of BRCA mutation (BRCAm) testing patterns, clinical characteristics and overall survival (OS) in breast cancer (BC) patients over a 20-year period.
Authors: David D. Stenehjem, Jerzy Tyczynski, Sudhir K. Unni, Hillevi Bauer, Amy Sainski, Rishi Deka, Marisa Schauerhamer, Lia Gutierrez, James A. Kaye, Claire Telford, Diana I. Brixner, Joseph E. Biskupiak
Journal: Journal of Clinical Oncology (2015)

e12518 Background: BRCAm are implicated in 5% of BC. Since PARP inhibitors may be preferentially active in BRCAm carriers with BC, we evaluated historical BRCAm testing patterns, clinical characteristics, and OS in BC patients stratified by BRCAm status. Methods: Patients with BC treated at the University of Utah Huntsman Cancer Institute (HCI) from 1995-2014 were identified from an institutional tumor registry linked to the Enterprise Data Warehouse. Germline BRCAm status was ascertained by chart review. Univariate COX regression models evaluated relationships between BRCAm and OS from BC diagnosis. Results: Study had 5712 BC patients with BRCAm testing reported in 918 (16.1%). Testing increased from 4.7% in 1995-1999 to 26.2% in 2010-2014, p < 0.001. A total of 153 (16.7%) were BRCAm+ (BRCA1 [n = 64, 41.8%], BRCA2 [n = 78, 51.0%], BRCA1 and BRCA2 [n = 2, 1.3%], and specific BRCAm not reported in 5.9% [n = 9]) and 765 were BRCAm-. Median age at BC diagnosis was 47 and 48 years in BRCAm+ and BRCAm- patients. Of those with known date of testing (n = 590, 64%), BRCA testing was conducted before BC diagnosis in 6.3% (n = 37; [more BRCAm+ vs BRCAm-, 13.3% vs 4.9%, p = 0.012]), within 90 days in 48.5% (n = 286), and ≥ 90 days post BC diagnosis in 45.3% (n = 267). No differences between groups were observed in ethnicity or stage at diagnosis. Triple negative BC (TNBC) was more common in BRCAm+ patients (24%, n = 36 vs 9%, n = 66; p < 0.001) and more common in BRCA1 (n = 24, 66.7%) vs BRCA2 (n = 10, 27.8%), p = 0.003. No difference in crude OS was observed between BRCAm+ vs BRCAm- (HR 1.19, 95% CI 0.66-2.04, p = 0.553) and BRCA1 vs BRCA2 (HR 0.56, 95% CI 0.17-1.68, p = 0.303). However, a trend for decreased OS was observed in metastatic BRCAm+ (n = 7) vs BRCAm- (n = 26) patients, (HR 2.4, 95% CI 0.72-7.16, p = 0.145). Conclusions: BRCA testing increased over time and was conducted in 26% of BC patients by the end of the study period, with most tested after BC diagnosis. BRCAm were detected in ~3% of the BC population and in 17% of tested patients. TNBC was more common in BRCAm+, correlated with BRCA1 mutations. The preliminary finding that OS does not differ according to BRCAm+/- or BRCA1/2 warrants further investigation.