tbuckley/cabot-search huggingface dataset:
Clarification of Reporting of Potential Conflicts of Interest in <i>JAMA</i> Articles
Authors: Andrew Kolodny
Journal: JAMA (2019)

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
The Public Health Urgency of a Temporary FDA Moratorium on New Opioid Approvals
Authors: Sidney M. Wolfe
Journal: JAMA Internal Medicine (2019)

This Viewpoint suggests the US Food and Drug Administration (FDA) halt approval of new opioids until the agency adopts a more rigorous framework for opioid review, providing 2 examples of new opioids that were approved by the FDA but had high rates of abuse after entering the drug market.
The Origin and Pathogenesis of Endometriosis
Authors: Yeh Wang, Kristen Nicholes, Ie-Ming Shih
Journal: Annual Review of Pathology Mechanisms of Disease (2019)

Recent molecular genetic findings on endometriosis and normal endometrium suggest a modified model in which circulating epithelial progenitor or stem cells intended to regenerate uterine endometrium after menstruation may become overreactive and trapped outside the uterus. These trapped epithelium-committed progenitor cells form nascent glands through clonal expansion and recruit polyclonal stromal cells, leading to the establishment of deep infiltrating endometriosis. Once formed, the ectopic tissue becomes subject to immune surveillance, resulting in chronic inflammation. The inflammatory response orchestrated by nuclear factor-κB signaling is exacerbated by aberrations in the estrogen receptor-β and progesterone receptor pathways, which are also affected by local inflammation, forming a dysregulated inflammation-hormonal loop. Glandular epithelium within endometriotic tissue harbors cancer-associated mutations that are frequently detected in endometriosis-related ovarian cancers. In this review, we summarize recent advances that have illuminated the origin and pathogenesis of endometriosis and have provided new avenues for research that promise to improve the early diagnosis and management of endometriosis.
Bioengineered adipose-derived stem cells for targeted enzyme-prodrug therapy of ovarian cancer intraperitoneal metastasis
Authors: Obeid M. Malekshah, Siddik Sarkar, Alireza Nomani, Niket Patel, Parisa Javidian, Michael Goedken, Marianne Polunas, Pedro Louro, Arash Hatefi
Journal: Journal of Controlled Release (2019)
OS8.8 Modified chromatin histone marks at noncoding elements are associated with aggressive meningioma subtype
Authors: T Malta, T Sabedot, I Lee, M Wells, A Castro, H Noushmehr
Journal: Neuro-Oncology (2019)

Abstract Background: Although most meningiomas are non-malignant, there is a high recurrence rate among atypical and anaplastic (malignant) meningiomas (grades II/III). In addition, malignant meningioma usually progresses after treatment. Recently, based on DNA methylation, two subgroups of meningioma were described with recurrence-free survival differences (favorable and unfavorable). Epigenetic deregulation at distinct genomic elements such as enhancers can drive changes in gene expression and alter the transcriptional profile of the cancer cells. We seek to understand the mechanisms of meningioma recurrence and progression after initial treatment. Material and Methods: Two favorable and two unfavorable meningioma high grade tumor tissue were selected for this pilot study. Immunoprecipitation (Antibodies) for two different histone modifications (H3K4me3 and H3K27ac) were used to generate genome-wide chromatin-IP sequencing. Genome-wide DNA methylation profile was assessed for 90 meningioma cases including the four samples used in this pilot study. Results: Using a FDR cutoff of 5%, we identified 10,049 H3K27ac and 5,752 H3K4me3 chromatin marks that distinguish favorable from unfavorable meningioma. We dichotomized the results into genomic regions overlapping known gene promoters and non-promoters. Promoter associated chromatin changes (H3K27ac and H3K4me3) coincide with DNA methylation changes in aggressive meningioma. The top 1,000 H3K27ac (sorted by fold difference) without H3K4me3 coincide with highly conserved DNA elements known to be associated with enhancers. These enhancers can drive expression of multiple genes simultaneously. Using DNA methylation differences between favorable and unfavorable meningioma, we will overlap with our unfavorable associated enhancers in order to refine our candidate enhancers for follow up mechanistic studies using aggressive meningioma cell lines. Conclusion: Our preliminary results are the first to unravel the genome-wide chromatin changes associated with unfavorable or clinically aggressive meningioma. Identification of these candidate enhancers will provide knowledge of the role of epigenomics in the development of malignant meningioma and of opportunities for targeted therapy. This project is supported by the Henry Ford Health System, Department of Neurosurgery and the Hermelin Brain Tumor Center Foundation (A30935), United States National Institutes of Health (R01CA222146), and United States Department of Defense (CA170278)
Survival Improvement in Therapy Related Myeloid Neosplasm ? a Single Center Analysis of 428 Patients
Authors: Khalil Saleh, Christophe Willekens, Jean Edouard Martin, Myriam Kossai, Nadine Khalifé-Saleh, Véronique Saada, Nathalie Auger, Alina Danu, Julien Lazarovici, Alexandra Leary, Suzette Delaloge, Jean Henri Bourhis, Éric Solary, Serge Koscielny, Stephane de Botton, Jean-Baptiste Micol
Journal: Blood (2016)
P14.114 Tumor treating fields in glioblastoma clinical practice guidelines: a European and North American landscape analysis
Authors: A Lawson McLean, R Kalff, J Walter
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Tumor treating fields (TTFields) are low-intensity alternating electric fields delivered at intermediate frequencies to disrupt cancer cell division and inhibit tumor growth, with significantly longer mean lifetime survival of 1.8 additional years in glioblastoma (GBM). International, national and local clinical practice guidelines have implications for clinical, personal and policy decision-making. Furthermore, they may impact on patients’ decisions to choose treatment at a given institution or even lead to commencement of legal proceedings for withholding therapies recommended by international guidelines. We performed an in-depth landscape analysis of clinical practice guidelines for GBM in Europe and North America to explore variation in treatment recommendations with a specific focus on TTFields. MATERIAL AND METHODS A systematic search was conducted of web sites of international guideline developers, relevant cancer agencies and the MEDLINE and Web of Science literature databases. The following information was extracted from each document meeting the inclusion criteria: whether TTFields is discussed and/or recommended in the guideline, the indications for and role of TTFields in the care protocol, the strength of the recommendation and any constraints placed on the situations where this therapy can or may be offered, including on cost grounds, where applicable. Dates of production and validity periods of the guidelines were also noted. In addition, standard operating procedures (SOPs) from several accredited comprehensive cancer centres in Germany, covering GBM care are compared, with a series of clinical vignettes presented. RESULTS The guidelines produced by the National Comprehensive Cancer Network (USA), National Institute for Health and Care Excellence (UK), German Society for Neurology, German Society for Haematology and Medical Oncology, European Association for Neuro-Oncology and European Society for Medical Oncology were critically compared. Wide variation in recommendations relating to the TTFields therapy was observed. Many guidelines had not been updated to reflect the results of the EF-14 study. CONCLUSION Discrepancy in the adoption of TTFields across clinical practice guidelines and SOPs has potential implications for care practices. This ultimately affects patient outcomes, safety and quality of care. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. An ongoing revision process for guidelines, perhaps with shorter validity periods or a more flexible approach, may facilitate more expedient adoption of novel therapies in clinical practice guidelines and in practice. Meanwhile, therapies significantly improving OS and PFS should be recommended to patients and this should be documented.
Phase II Study of High Dose Cytarabine Followed By Pembrolizumab in Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Joshua F Zeidner, Benjamin G. Vincent, Anastasia Ivanova, Matthew Foster, Catherine C. Coombs, Katarzyna Jamieson, Hendrik Van Deventer, Richard Scibilia, Laura Blanchard, Cassiopeia Frank, Sean Gallagher, Melissa Matson, Katherine Pepin, Lori Vaught, Nancy Vogler, Ivana Gojo, Leo Luznik, Jonathan S Serody
Journal: Blood (2017)
In vivo activation of PEGylated long circulating lipid nanoparticle to achieve efficient siRNA delivery and target gene knock down in solid tumors
Authors: Yumi Sasayama, Maki Hasegawa, Eri Taguchi, Kohei Kubota, Takeshi Kuboyama, Tomoyuki Naoi, Hayato Yabuuchi, Norie Shimai, Miyoko Asano, Akihiro Tokunaga, Toshihiko Ishii, Junichi Enokizono
Journal: Journal of Controlled Release (2019)
P12.03 Bi-specific T cell engagers targeting IL13Rá2 activate tumor-infiltrating lymphocytes and improve survival in pre-clinical models of glioblastoma
Authors: M Zannikou, K C Pituch, L Ilut, I V Balyasnikova
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The outstanding efficacy of bi-specific T-cell engagers (BiTE against hematological malignancies offers hope that they can similarly target solid tumors like GBM. In this study, we have designed a BiTE protein with specificity to the tumor-associated antigen, IL13Rα2, and investigated how BiTE protein engages a host’s T cell immune response to promote anti-glioma activity in pre-clinical models of GBM. MATERIAL AND METHODS BiTE molecule consisting of two single chain variable regions (scFv) of antibodies against either murine or human CD3ε and scFv47 against human IL13Rα2 connected through a flexible linker (BiTEIL13Rα2) were sub-cloned in a lentiviral expression cassette. The BiTE molecule (BiTEIL13Rα2off) modified to abrogate the interaction of scFv47 with IL13Rα2 served as a negative control. The BiTE proteins were isolated from the supernatants of HEK293T cells using His-Tag affinity chromatography and validated in SDS-PAGE, Western Blot, and ELISA assays. The BiTEIL13Rα2-induced T cells activation was measured in (i) cytotoxicity assay against IL13Rα2+ glioma cells, (ii) flow cytometry measuring for CD69 and CD25 T cells’ activation markers, and (iii) the production of cytokines, IFNγ and TNFα. For in vivo analysis, VmDk and C57Bl/6 mice bearing established intracranial glioma were treated systemically with BiTE proteins. The survival of the mice was recorded and analyzed using the log-rank test. RESULTS Here we show that BiTEIL13Rα2 specifically binds to IL13Rα2 but not to IL13Rα1, whereas BiTEIL13Rα2off has no binding activity to both IL13 receptors. The co-culture of naïve murine or donor’s human CD3+ T cells with IL13Rα2+ glioma cells in the presence of BiTEIL13Rα2 but not with BiTEIL13Rα2off (i) activates CD3+CD8+ T cells as judged by upregulation of CD69, CD25, and production of IFNγ and TNFα and (ii) results in concentration- and antigen-dependent cytotoxicity in glioma cells. Furthermore, a direct comparison of CD3+ T cells obtained from the peripheral blood and tumor tissue of GBM patients revealed that BiTEIL13Rα2 induces a potent cytotoxic activity of CD3+ T cells against IL13Rα2+ glioma cells. Finally, treatment of immunocompetent mice bearing IL13Rα2+ murine glioma with BiTEIL13Rα2 resulted in a higher frequency of intratumoral CD8+ T cells, and significant (p&lt;0.05) improvement of survival over a negative control, BiTEIL13Rα2off group of mice. CONCLUSION Our data demonstrate that BiTEIL13Rα2 protein activates CD3+ T cells in an antigen-specific fashion. Furthermore, systemic treatment with BiTEIL13Rα2 protein confers a significant survival benefit in pre-clinical syngeneic glioma models, warranting investigations in other IL13Rα2-expressing cancers and translation to clinical settings.
LncRNA SATB2-AS1 inhibits tumor metastasis and affects the tumor immune cell microenvironment in colorectal cancer by regulating SATB2
Authors: Mu Xu, Xueni Xu, Bei Pan, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Tao Xu, Li Sun, Jian Qin, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang
Journal: Molecular Cancer (2019)

Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we report a lncRNA, SATB2-AS1, which is specifically expressed in colorectal tissue and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanisms in CRC. LncRNA expression in CRC was analyzed by RNA-sequencing and RNA microarrays. The expression level of SATB2-AS1 in tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). The functional role of SATB2-AS1 in CRC was investigated by a series of in vivo and in vitro assays. RNA pull-down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), chromatin isolation by RNA purification (ChIRP), Bisulfite Sequencing PCR (BSP) and bioinformatics analysis were utilized to explore the potential mechanisms of SATB2-AS1. SATB2-AS1 is specifically expressed in colorectal tissues and downregulated in CRC. Survival analysis indicates that decreased SATB2-AS1 expression is associated with poor survival. Functional experiments and bioinformatics analysis revealed that SATB2-AS1 inhibits CRC cell metastasis and regulates TH1-type chemokines expression and immune cell density in CRC. Mechanistically, SATB2-AS1 directly binds to WDR5 and GADD45A, cis-activating SATB2 (Special AT-rich binding protein 2) transcription via mediating histone H3 lysine 4 tri-methylation (H3K4me3) deposition and DNA demethylation of the promoter region of SATB2. This study reveals the functions of SATB2-AS1 in CRC tumorigenesis and progression, suggesting new biomarkers and therapeutic targets in CRC.
Bevacizumab (Bev), irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): The SICOG experience
Authors: P. Comella, B. Massidda, D. Natale, G. Filippelli, A. Farris, G. Condemi, S. Palmeri, S. Tafuto, G. Vessia, G. Barberis
Journal: Journal of Clinical Oncology (2009)

e15067 Background: The IRIFAFU regimen produced in MCRC pts a consistent activity (RR, 33% [95% CI, 27–39%], PFS, 7.4 [95% CI, 6.5–8.3] mo.) in 2 consecutive randomized SICOG trials . Bev was proven to significantly improve the efficacy of IFL regimen. Here we report the safety and activity results of the BIFF regimen as first-line treatment of MCRC. Patients: From Feb 2007 to Jul 2008, 95 pts with MCRC were treated: so far, 85 pts were evaluated for safety: M/F were 47/38, median age (range) was 64 (35–78) yrs. Fifty-six pts had a colon, and 29 pts a rectal carcinoma. ECOG PS was 0 (63 pts, 74%), or 1 (22 pts, 26%). Thirty-four (40%) pts had 1 site, 33 (39%) 2 sites, and 18 (21%) pts ≥3 sites of disease. Liver was involved in 66 (78%), lung in 23 (24%) pts. Twenty-one (25%) pts had an unresected primary (colon 13, rectum 8). Bev 5 mg/kg (1-h), and IRI 180 mg/sqm (1-h) were given IV on day 1, 6S-FA 250 mg/sqm (2-h), and FU 850 mg/sqm (bolus) were given IV on day 2 biweekly for a maximum of 12 cycles. Bev was continued until progression, severe toxicity, or refusal. Results: A median of 9 (range, 1–12) cycles of BIFF were delivered. G4 hematologic toxicity was: neutropenia (21%), and febrile neutropenia (10%). G≥3 non-hematologic toxicity was: diarrhea 15%, vomiting 7%, stomatitis 4%, hypertension 1%. No severe episodes of bleeding were registered. Among 81 assessable pts, 5 CRs (3 in liver, 1 in liver &amp; nodes, 1 in liver &amp; lung), and 41 PRs were registered, giving a RR of 57% (95% CI, 45–68%). Overall, 71/81 (88%, 95% CI, 77–93%) pts obtained a disease control. Liver mets resection, or primary resection, was safely performed in 3 pts and in 2 pts, respectively. After a median follow- up of 12 (range, 6–24) mo., median FFS was 8.4 (95% CI, 6.8–10.0), and median PFS was 14.1 (95% CI, 9.6–18.6) mo. With only 14 deaths, OS results are still immature. Conclusions: Unexpected side effects of the BIFF regimen were not registered. Addition of Bev increased the activity without worsening the tolerability of IRIFAFU combination as compared with our previous experience. Efficacy of BIFF was comparable with that reported with other Bev plus IRI-based combinations. Updated follow-up will be presented. No significant financial relationships to disclose.
Environmental effects on head and neck cancer in India
Authors: A. Mishra, V. P. Singh, V. Verma
Journal: Journal of Clinical Oncology (2009)

e17059 Background: Head and neck cancer in India has unique demographic profile, environmental exposure, dietary habits, and personal and family history. Methods: 1,000 cases were analysed. Results: Males dominated (82%) in fifth (29%) and sixth (33%) decades. Majority was uneducated (76%) and poor. Passive tobacco smoking was seen in-house (85%) as well as in the work-place (80%). Approximately 69% smoked more than 100 cigarettes/bidis in their lifetime. Majority acquired regular smoking habit in second (73%) and third (18%) decades and continued smoking for more than 20 years (66%) with 10–20 cigarettes daily (range 1 to 43). However 30% never used tobacco. The main alternative forms were bidi (27%) and smokeless-tobacco chewing products (47%). A past history of cancer and the subsequent radiation treatment was found in 3% while GERD in 33%. Multivitamins/minerals for chemoprevention was used in 65% for 1 to 12 months. Alcohol consumption was seen in 26% where the age of initiation was in second and third decade and the total years of consumption mainly varied from 10–30 years. Having a predominant agriculture-based-economy, the majority of males (38%) were farmers with significant exposure to pesticides and fertilizers; while females predominantly housewifes (17%). The family history was appreciated in 1% with natural parents known in all. The most common sites involved were oral cavity (28%), oropharynx (30%), and larynx (32%). Majority presented with advanced stage (III = 39%; IV = 23%). The consumption of fruit and vegetable juice was less common as compared to fresh consumption as such. Green salads, potatoes, and fiber cereals were significantly used (4–6 times a week). Beans, peas, and corn was not common while beef and pork consumption rare owing . The ‘staple’ diet was wheat, rice, pulses with additional meat mainly in Muslims (once a day). The use of cooking oil, butter, eggs biscuits, cheese, cakes, and cookies was uncommon (less than once a week), but milk was abundant. Conclusions: Hence, it seems that poor, education/literacy, poor socioeconomic status, tobacco smoking (passive and active) at an early age for prolonged duration, tobacco-related products and exposure to pesticides/fertilizers predispose Indian population for head and neck cancer, rather than a positive family history, dietary factors, radiation exposure, or alcoholism. No significant financial relationships to disclose.
Stress-induced remodelling of the mitral valve: a model for leaflet thickening and superimposed tissue formation in mitral valve disease
Authors: Boudewijn P T Kruithof, Laura Paardekooper, Yasmine L Hiemstra, Marie-José Goumans, Meindert Palmen, Victoria Delgado, Robert J M Klautz, Nina Ajmone Marsan
Journal: Cardiovascular Research (2019)

In mitral valve prolapse (MVP), leaflet thickening has recently been suggested to be due, in addition to a myxomatous degeneration, to the presence of a superimposed tissue (SIT), defined as an additional fibrous layer on top of the original leaflet. The mechanisms of SIT formation are currently unknown. We hypothesized that SIT formation would result from excessive leaflet stress and we used a unique ex vivo model to assess the correlation between leaflet remodelling and the type and location of mechanical stress and to elucidate the mechanisms underlying SIT formation.Human diseased mitral valves (MVs; n = 21) were histologically analysed for SIT formation and original leaflet thickening. The SIT comprised of various compositions of extracellular matrix and could reach more than 50% of total leaflet thickness. Original leaflet and SIT thickness did not show significant correlation (r = -0.27, P = 0.23), suggesting different regulatory mechanisms. To study the role of the mechanical environment on MV remodelling, mouse MV were cultured in their natural position in the heart and subjected to various haemodynamic conditions representing specific phases of the cardiac cycle and the MVP configuration. SIT formation was induced in the ex vivo model, mostly present on the atrial side, and clearly dependent on the duration, type, and extent of mechanical stress. Specific stainings and lineage tracing experiments showed that SIT comprises of macrophages and myofibroblasts and is associated with the activation of the transforming growth factor-beta and bone morphogenetic protein signalling pathways. Migration of valvular interstitial cells and macrophages through breakages of the endothelial cell lining contributed to SIT formation.Mechanical stresses induce specific cellular and molecular changes in the MV that result in SIT formation. These observations provide the first insights in the mechanism of SIT formation and represent an initial step to identify potential novel and early treatment for MVP.