tbuckley/cabot-search huggingface dataset:
A phase II open-label, single-centre, non-randomized trial of Y90 transarterial radioembolization in combination with nivolumab in Asian patients with intermediate stage hepatocellular carcinoma: An immunological study of radioembolization in combination with anti-PD1 therapy in HCC.
Authors: Esther Wei Yin Chang, David Wai-Meng Tai, Si-Lin Koo, Matthew CH Ng, Joe Poh Sheng Yeong, Wei Wei Zhai, Evan Newell, Pierce K. H. Chow, Kiat Hon Lim, Apoorva Gogna, Aaron Kian Ti Tong, Hian Liang Huang, Kelvin Siu Hoong Loke, David Chee Eng Ng, Tiffany Priyanthi Hennedige, Choon Hua Thng, Su Pin Choo
Journal: Journal of Clinical Oncology (2018)

TPS542 Background: In recent years, Yttrium-90 (Y90) trans-arterial radioembolization (TARE) has emerged as a therapeutic option for intermediate stage hepatocellular carcinoma (HCC). Cancer immunotherapy targeting tumour immune evasion has shown remarkable successes in various cancers. Nivolumab, an immune checkpoint inhibitor of programmed death 1 (PD1), has demonstrated encouraging activity in advanced stage HCC. Similarly, chronic hepatitis B virus (HBV) infection, a strong risk factor for HCC, is characterized by immune escape mechanisms. We hypothesize that TARE will stimulate tumor and/or HBV specific T cell responses that can be boosted using nivolumab. We thus propose an open label phase 2 trial investigating the combination of TARE with nivolumab in BCLC intermediate stage HCC. Methods: Eligible patients (pts) have ECOG performance status ≤ 2, Child-Pugh A score, intermediate stage HCC planned for TARE according to institutional practice with adequate organ function. Pts will be treated with TARE followed by nivolumab 240mg, 21 days after TARE and every 2 weeks thereafter. Pre- and on-treatment tumor biopsies will be taken. Primary end-point is response rate (RR) of combinational TARE and nivolumab. Key secondary end points are: progression free survival, overall survival, safety and quality of life using FACT-HEP score and EORTC QLQ-C30. Exploratory objectives are to evaluate how tumor PD L-1 expression, HCC mutational burden and blood lymphocyte activation/phenotypic profiles correlate with tumor response. Where possible, serial changes in antigen-specific T cell responses to HBV and/or tumour antigens will also be assessed. This study aims to enroll 40 pts as calculated using the Simon two-stage optimal design with 80% power and one sided significance level of 0.05. This will assess whether the addition of nivolumab improves the RR of TARE at 8 weeks from 21% to 41%. Patient accrual was initiated in December 2016 and as of September 2017, 9 pts have been treated. Clinical trial information: 03033446.
Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway
Authors: Chao Yu, Shiyu Chen, Yuntao Guo, Chengyi Sun
Journal: Theranostics (2018)

Background: Drug resistance is well known as a major obstacle for cancer recurrence and treatment failure, leading to poor survival in pancreatic cancer, which is a highly aggressive tumor.Identifying effective strategies to overcome drug resistance would have a significant clinical impact for patients with pancreatic cancer.Methods: The protein and mRNA expression of TRIM31 in pancreatic cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively.89 human pancreatic cancer tissue samples were analyzed by IHC to investigate the association between TRIM31 expression and the clinicopathological characteristics of pancreatic cancer patients.Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM31 in human pancreatic cancer progression.Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM31 promotes chemoresistance in pancreatic cancer cells.Results: The expression of TRIM31was markedly upregulated in pancreatic cancer cell lines and tissues, and high TRIM31 expression was associated with an aggressive phenotype and poor prognosis with pancreatic cancer patients.TRIM31 overexpression confers gemcitabine resistance on pancreatic cancer cells; however, inhibition of TRIM31 sensitized pancreatic cancer cell lines to gemcitabine cytotoxicity both in vitro and in vivo.Additionally, TRIM31 upregulated the levels of nuclear p65 by promoting K63-linked polyubiquitination of tumor necrosis factor receptor-associated factor 2 (TRAF2) and sustained the activation of nuclear transcription factor kappa B (NF-κB) in pancreatic cancer cells.Conclusions: Our findings provided evidence that TRIM31 is a potential therapeutic target for patients with pancreatic cancer.Targeting TRIM31 signaling may be a promising strategy to enhance gemcitabine response during pancreatic cancer chemo-resistance.
Glucocorticoid‐induced eosinopenia in humans can be linked to early transcriptional events
Authors: P. Khoury, K. Stokes, M. Gadkari, M. A. Makiya, F. Legrand, Z. Hu, A. Klion, L. M. Franco
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism
Authors: Angelina V. Vaseva, Devon R. Blake, Thomas S.K. Gilbert, Serina Ng, Galen Hostetter, Salma H. Azam, Irem Ozkan-Dagliyan, Prson Gautam, Kirsten L. Bryant, Kenneth H. Pearce, Laura E. Herring, Haiyong Han, Lee M. Graves, Agnieszka K. Witkiewicz, Erik S. Knudsen, Chad V. Pecot, Naim Rashid, Peter J. Houghton, Krister Wennerberg, Adrienne D. Cox, Channing J. Der
Journal: Cancer Cell (2018)
Questioning the Associations of ω-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks
Authors: Arrigo F. G. Cicero, Federica Fogacci, Claudio Borghi
Journal: JAMA Cardiology (2018)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
The integrated genomic and immune landscapes of lethal metastatic breast cancer (MBC).
Authors: Leticia De Mattos-Arruda, Stephen-John Sammut, Edith M Ross, Rachael Bashford-Rogers, Erez Greenstein, Sandro Morganella, Oscar M Rueda, Elena Martinez-Saez, Vicente Peg, Javier Cortés, Serena Nik-Zainal, Muhammed Murtaza, Nir Friedman, Florian Markowetz, Joan Seoane, Carlos Caldas
Journal: Journal of Clinical Oncology (2018)

1009 Background: The heterogeneous fates of MBC preclude our understanding of both resistance to therapy and escape from cancer immunoediting. Here, we performed a comprehensive molecular analysis of lethal MBC patients (pts), interrogating both the malignant and immune tumor microenvironment (TME) compartments, and T-cell receptor (TCR) repertoires, across multiple metastases (mets). Methods: Multi-platform profiling of mets (N = 182 mets to 22 organs, 5-36 mets/pt), primary tumors (pr) (N = 6) and ctDNA from body fluids (4.7/pt) in 10 warm autopsies of MBC pts (5 ER+/HER2-, 3 ER+/HER2+, 1 ER-/HER2+, 1 ER-/HER2-), included exome seq (N = 86), shallow whole genome seq (N = 168), RNA seq (N = 61), ultra-deep targeted seq (TS) (N = 243), TCRseq (N = 70) and IHC (N = 102). State-of-the-art bioinformatics was applied to the data. Results: Mutation (mut) burden landscape varied between pts (11,579 mut, median 255.41 mut/pt) and across mets within each pt (median 122 mut/met); was greater than TCGA mut burden (median 63.5 mut/pr, p = 4.927e-14). Landscape of mut and predicted neo-antigen were dominated by stem (present in all mets/pt) or clade (some mets/pt), but not private (one met/pt). TS data confirmed that all pr tumors contained the clonal ancestors of 10 pts, and characterized ctDNA bathing organs. Copy number alteration profiles were remarkably similar across mets in 9 of the 10 pts, except in a ER+/HER2- pt, whose mets shared a common ancestor (1q gain/16q loss), then early sub-clonal evolution occurred. Mets were grouped into phylogenic clades that share common genomic ancestry and accumulated previously unknown mutation signatures. Mets evolved as communities of clones as a fraction of the metastatic stem and clade mutations were sub-clonal. Immune TME was either homogeneous in a particular metastatic clade, or different across mets to a particular organ. Stem and clade clonotypes prevailed across TCR landscape within each pt. TCR repertoires revealed adaptive immune responses to co-evolve with the metastatic genomes. Conclusions: The genomic and immune landscapes demonstrate an unprecedented integrated view of the heterogeneous landscape of genomic aberrations, TME features and T-cell adaptive immune responses in lethal MBC.
Risks and Benefits of Antenatal Late-Preterm Corticosteroids
Authors: Joshua I. Rosenbloom, Adam K. Lewkowitz, Methodius G. Tuuli
Journal: JAMA Pediatrics (2018)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Abstract 4188: RNAi and CRISPR/Cas9 basedin vivomodels for drug discovery
Authors: Prem K. Premsrirut, Gregory Martin, Lukas Dow, Sang Yong Kim, Johannes Zuber, Scott Lowe, Greg Hannon
Journal: Cancer Research (2016)

Abstract With the advent of CRISPR-Cas9 technology, the speed and precision in which genetically engineered mouse models can be created is unprecedented. We now have at our disposal a genetic toolbox that will enable the rapid generation of sophisticated mouse models of cancer. Recently, an inducible CRISPR-Cas9 (iCRISPR) system was described that enables doxycycline-regulated Cas9 induction of widespread gene mutagenesis in multiple tissues. Previously, we also demonstrated how inducible RNA interference (RNAi) can be exploited experimentally to effectively and reversibly silence nearly any gene target not only in vitro but also in live mice. Here, we take advantage of these powerful technologies and combine both tet-inducible CRISPR-Cas9 and inducible RNAi-mediated gene silencing to develop animal models in which both de novo tumorigenesis can be induced by Cas9-mediated genome editing and therapeutic strategies assessed downstream via RNA interference-mediated gene silencing. By using this combination of CRISPR/Cas9 and RNAi technologies, we are able to not only model disease pathogenesis, but also mimic drug therapy in the same mice, giving us exceptional capabilities to perform preclinical studies in vivo. Using our robust flexible system, we have created a cost-effective and scalable platform for the production of complex genetically engineered mouse models of cancer with RNAi silencing of nearly any gene - mice with enormous predictive power that will shape our development of better tolerated therapies. Citation Format: Prem K. Premsrirut, Gregory Martin, Lukas Dow, Sang Yong Kim, Johannes Zuber, Scott Lowe, Greg Hannon. RNAi and CRISPR/Cas9 based in vivo models for drug discovery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4188.
Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment
Authors: M. Garofalo, H. Saari, P. Somersalo, D. Crescenti, L. Kuryk, L. Aksela, C. Capasso, M. Madetoja, K. Koskinen, T. Oksanen, A. Mäkitie, M. Jalasvuori, V. Cerullo, P. Ciana, M. Yliperttula
Journal: Journal of Controlled Release (2018)

Standard of care for cancer is commonly a combination of surgery with radiotherapy or chemoradiotherapy. However, in some advanced cancer patients this approach might still remaininefficient and may cause many side effects, including severe complications and even death. Oncolytic viruses exhibit different anti-cancer mechanisms compared with conventional therapies, allowing the possibility for improved effect in cancer therapy. Chemotherapeutics combined with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. Here, we have investigated the systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV) formulation that, in vitro, significantly increased the transduction ratio and the infectious titer when compared with the virus and paclitaxel alone. We demonstrated that the obtained EV formulation reduced the in vivo tumor growth in animal xenograft model of human lung cancer. Indeed, we found that combined treatment of oncolytic adenovirus and paclitaxel encapsulated in EV has enhanced anticancer effects both in vitro and in vivo in lung cancer models. Transcriptomic comparison carried out on the explanted xenografts from the different treatment groups revealed that only 5.3% of the differentially expressed genes were overlapping indicating that a de novo genetic program is triggered by the presence of the encapsulated paclitaxel: this novel genetic program might be responsible of the observed enhanced antitumor effect. Our work provides a promising approach combining anticancer drugs and viral therapies by intravenous EV delivery as a strategy for the lung cancer treatment.
Sun exposure profile in the French population: Results of the EDIFICE melanoma survey.
Authors: Bruno Sassolas, Florent Grange, Chantal Touboul, Celeste Lebbe, Philippe Saiag, Laurent Mortier, Christine Lhomel, Caroline Robert
Journal: Journal of Clinical Oncology (2012)

1566 Background: The main environmental risk factor for melanoma is related to UV-exposure. Our objective was to evaluate in a survey the profile of sun exposition in the French population as well as the level of knowledge about UV risk and UV protection. Methods: “Edifice Melanoma” a nationwide observational survey was conducted in France via phone interviews among a representative sample of 1502 subjects aged ≥ 18, using the quota method. The survey took place shortly after the summer (September 28 th to October 20 th , 2011). Results: From the total population of 1502 subjects, 330 (22%) denied any sun exposition. Among those declaring being exposed to the sun (1172), 62% affirmed using a photoprotection method (clothes, sun protective cream). The opportunities for sun exposure arose during holidays (85%), sport (79%) or professional activities (23%), with an annual average exposure of 113 days. 902 subjects (77%) declared avoiding sun exposure between 12 and 4 PM. The main sociodemographic characteristics of subjects exposed to the sun, compared to non-exposed ones are as followed (p&lt;0,05): men, aged &lt;40, with no children or with children aged &lt;15, from high social and occupational group, with at least a 2-years university degree. The analysis of sociodemographic characteristics of subjects declaring to use sun protective measures are (p&lt;0,05): women from high social and occupational group, with at least a 2-years university degree, with high income levels. We explored additional risk behavior in the population studied. Subjects who declared having sun exposure were more likely (p&lt;0,05) to be : smokers, alcohol users and/or alcoholic, tanning bed users before the age of 30, and have a high number of nevi (&gt;50). On the other hand, prior history of cancer was associated with a non-exposure behavior. Conclusions: These data provide important new information about sun behavior in the French population and might give important clues in the field of public health and education to increase the effectiveness of melanoma primary prevention campaigns. A better knowledge of the target to improve would provide better results for public health benefit.
Correction to: Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling
Authors: Anthony S. Zannas, Janine Arloth, Tania Carrillo-Roa, Stella Iurato, Simone Röh, Kerry J. Ressler, Charles B. Nemeroff, Alicia K. Smith, Bekh Bradley, Christine Heim, Andreas Menke, Jennifer F. Lange, Tanja Brückl, Marcus Ising, Naomi R. Wray, Angelika Erhardt, Elisabeth B. Binder, Divya Mehta
Journal: Genome biology (2018)

Upon publication of the original article [1] it was highlighted by the authors that a transposition error affected Additional file 1, causing the misplacement of several columns and rendering the table difficult to read. This transposition does not influence any of the results nor analyses presented in the paper and has since been formally noted in this correction article; the corrected file is available here as an Additional File. The publisher apologizes for this error.
Voluntary Opioid Tapering—Barriers to Delivering Care
Authors: Michael E. Schatman, David J. DiBenedetto, Ronald J. Kulich
Journal: JAMA Internal Medicine (2018)

To the Editor We commend Dr Darnall and her colleagues for their recent investigation of voluntary opioid tapering.1 Although the authors provided a novel model for care, we believe that there exists considerable ground that still needs to be broken.
Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer and <i>EGFR</i>-Activating Mutations
Authors: Tony S. Mok, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Min Lee, Rolf Linke, Rafael Rosell, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Eric I. Sbar, Tao Wang, Jane Liang White, Yi-Long Wu
Journal: Journal of Clinical Oncology (2018)

Purpose ARCHER 1050, a randomized, open-label, phase III study of dacomitinib versus gefitinib in treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) and activating mutations in EGFR, reported significant improvement in progression-free survival with dacomitinib. The mature overall survival (OS) analysis for the intention-to-treat population is presented here. Patients and Methods In this multinational, multicenter study, patients age 18 years or older (≥ 20 years in Japan and Korea) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR (exon 19 deletion or exon 21 L858R) were enrolled and randomly assigned in a 1:1 manner to dacomitinib (n = 227) or gefitinib (n = 225). Random assignment was stratified by race (Japanese, Chinese, other East Asian, or non-Asian) and EGFR mutation type. The final OS analysis was conducted with a data cutoff date of February 17, 2017; at that time 220 deaths (48.7%) were observed. Results During a median follow-up time of 31.3 months, 103 (45.4%) and 117 (52.0%) deaths occurred in the dacomitinib and gefitinib arms, respectively. The estimated hazard ratio for OS was 0.760 (95% CI, 0.582 to 0.993; two-sided P = .044). The median OS was 34.1 months with dacomitinib versus 26.8 months with gefitinib. The OS probabilities at 30 months were 56.2% and 46.3% with dacomitinib and gefitinib, respectively. Preliminary subgroup analyses for OS that are based on baseline characteristics were consistent with the primary OS analysis. Conclusion In patients with advanced NSCLC and EGFR activating mutations, dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (TKI) to show significant improvement in OS in a phase III randomized study compared with a standard-of-care TKI. Dacomitinib should be considered one of the standard treatment options for these patients.
Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss
Authors: Courtney A. Schreiber, Mitchell D. Creinin, Jessica Atrio, Sarita Sonalkar, Sarah J. Ratcliffe, Kurt T. Barnhart
Journal: New England Journal of Medicine (2018)

Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).