tbuckley/cabot-search huggingface dataset:
GENT-49. SYSTEMATIC IDENTIFICATION OF ESSENTIAL LONG NON-CODING RNA GENES IN GLIOBLASTOMA
Authors: Siyuan Liu, Max Horlbeck, Seung Woo Cho, Harjus Birk, Martina Malatesta, Daniel He, Jacqueline Villalta, Min Cho, Yuwen Chen, Mohammad Mandegar, Michael Olvera, Bruce Conklin, Howard Chang, Jonathan Weissman, Daniel Lim
Journal: Neuro-Oncology (2016)

The human genome harbors many thousands of genes that produce long non-coding RNAs (lncRNAs)—transcripts >200 nucleotides long that do not appear to code for proteins. While it is now clear that specific lncRNAs can have critical biological roles, of the many thousands of known human lncRNA genes, only a very small fraction have been identified to have essential functions for the cell. Here we show CRISPR interference (CRISPRi) to be a readily scalable, highly specific technology for the systematic repression of lncRNA transcription. Using an improved CRISPRi targeting algorithm, we generated pooled single guide RNA (sgRNA) libraries targeting ~17,000 lncRNA genes and screened for those that are essential for robust proliferation of six different cancer cell lines including glioblastoma multiforme (GBM) as well as human induced pluripotent stem cells. We identified ~500 lncRNA genes essential for robust cell growth, the vast majority of which previously had no known function. Remarkably, over 85% of these lncRNAs were uniquely essential to just one cell line, and none were essential in all cell lines screened. This surprising cell type-specificity was far greater than could be predicted by lncRNA expression alone. Furthermore, RNA-seq following lncRNA knockdown revealed lncRNA-dependent transcriptional networks reflecting cell line-specific essential function. Knockdown of the same lncRNA in other cell lines resulted in minimal changes to the transcriptome beyond the lncRNA itself. Machine learning from our screen datasets identified genomic features that predict lncRNA essentiality in a given cell type. lncRNA essentiality could further be related to diverse mechanisms, including key differences in chromatin conformation and function of the lncRNA transcript itself. Broadly, the cell type specificity of essential lncRNAs greatly exceeds that of essential protein coding genes and provides new opportunities for understanding and therapeutically targeting specific tumors types such as GBM.
Testosterone attenuates group 2 innate lymphoid cell cytokine expression and innate immune-mediated airway inflammation
Authors: Jacqueline Cephus, Matt T. Stier, Hubaida Fuseini, Shinji Toki, Melissa H. Bloodworth, Weisong Zhou, Kasia Goleniewska, Jian Zhang, Kelli L. Boyd, Stokes Peebles, Dawn C. Newcomb
Journal: Journal of Allergy and Clinical Immunology (2017)
Clinical impact of extensive molecular profiling in advanced cancer patients
Authors: Sophie Cousin, Thomas Grellety, Maud Toulmonde, Céline Auzanneau, Emmanuel Khalifa, Yec’han Laizet, Kevin Tran, Sylvestre Le Moulec, Anne Floquet, Delphine Garbay, Jacques Robert, Isabelle Hostein, Isabelle Soubeyran, Antoine Italiano
Journal: Journal of Hematology & Oncology (2017)

Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0–9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19–88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3. Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.
Bevacizumab versus bevacizumab plus vorinostat in adults with recurrent malignant glioma: Results of a phase I part of a phase I/II trial.
Authors: Jing Wu, Morris D. Groves, Mark R. Gilbert, Kenneth R. Hess, Carolyn Sue Loch, Sandra Ictech, John Frederick De Groot, Charles A. Conrad, W. K. Alfred Yung, Vinay K. Puduvalli
Journal: Journal of Clinical Oncology (2012)

2029^ Background: Antiangiogenic therapy using b evacizumab (Bev) has shown promising activity against recurrent glioblastoma (GBM). However, most patients have disease progression after striking but transient responses. Salvage therapies have been uniformly ineffective, suggesting development of resistance mechanisms including upregulation of other proangiogenic factors and increased activity of hypoxia inducible factors (HIF)-1a. Vorinostat, a histone deacetylase (HDAC) inhibitor has single agent activity against recurrent GBM and downregulates HIF-1a and other proangiogenic and invasive factors. We hypothesized that HDAC inhibition combined with Bev would result in improved clinical outcome. We report the results of the Phase I portion of the study preceding the initiation of the 2-arm adaptive randomized Phase II study. Methods: Adults with recurrent malignant glioma, KPS ≥ 60, normal hepatic, renal and marrow organ function and no prior exposure to Bev or Vorinostat were enrolled to the combination therapy after the confirmation of recurrent GBM. A conventional 3+3 Phase I design was used to determine the maximum tolerated dose (MTD) and the toxicity profile of the combination of Bev and Vorinostat. The starting dose was Bev at 10mg/kg administered on days 1 and 15 intravenously and Vorinostat 400 mg/day orally on days 1 to 7, and days 15 to 21 with each cycle being 28 days. Results: A total of 6 patients were enrolled and all 6 patients were evaluable. Three patients were enrolled in the first cohort at the starting dose of the combination and completed the first cycle. One patient experienced a grade 3 ALT elevation and grade 3 hyperglycemia, which were designated as possibly related to vorinostat and constituting a dose-limiting toxicity (DLT). No grade 4 toxicities were noted. The cohort was expanded by 3 more patients with none of these patients experienced a DLT in the first cycle. The starting dose level of Bev and v orinostat was declared the Phase II dose. Conclusions: Combination of Bev (10 mg/kg q 2 weeks) and of vorinostat (400 mg on days 1 to 7 and 15 to 21) has tolerable toxicity profile. This will be followed by a multicenter Bayesian adaptive randomized Phase II study.
Correlative Study of ZAP-70 Gene Expression by Quantitative PCR and CD-38 Surface Marker in Patients with Chronic Lymphocytic Leukemia (CLL).
Authors: Melissa L. Larson, Jamile M. Shammo, Sari H. Enschede, Parameswaran Venugopal, Daniel Russell, John S. Coon, Stephanie A. Gregory
Journal: Blood (2004)
Dual Inhibition of Canonical and Non-Canonical NF-KB Pathway Demonstrates Significant Anti-Tumor Activities in Multiple Myeloma (MM)
Authors: Claire Fabre, Naoya Mimura, Kathryn Bobb, Gullu Gorgun, Diana D. Cirstea, Yiguo Hu, Jiro Minami, Hiroto Ohguchi, Jie Zhang, Jeffrey Meshulam, Constantine S. Mitsiades, Paul G. Richardson, Teru Hideshima, Kenneth C. Anderson
Journal: Blood (2011)
Immorality of inaction on inequality
Authors: Kate E Pickett, Richard G Wilkinson
Journal: BMJ (2017)

Our collective failure to reverse inequality is at the heart of a global malaise 

Each year, at its meeting in Davos, the World Economic Forum produces a report on global risks, highlighting the biggest challenges the world is facing and the connections between them. Inequality entered the list of global risks in 2012, and in 2017 rising income and wealth disparity ranked as the most important trend likely to determine development across the world over the next decade.1 Oxfam also issues reports on inequality at Davos—in 2014 shocking the world with its estimate that the 85 richest people in the world owned as much wealth as the poorest 3.5 billion; this year reporting that just eight men own the same wealth as the poorest half of the world.23

During the 20th century inequality in most rich countries fell almost continuously from the 1930s to the 1970s and then increased dramatically from the 1980s with the dominance of neoliberal …
Erlotinib beyond progression study: Randomized phase II study comparing chemotherapy plus erlotinib with chemotherapy alone in EGFR tyrosine kinase inhibitor (TKI)-responsive, non-small cell lung cancer (NSCLC) that subsequently progresses.
Authors: Balazs Halmos, Nathan A. Pennell, Gregory Alan Otterson, Shirish M. Gadgeel, Tarek Mekhail, Michael Robert Snell, J. Phillip Kuebler, Pingfu Fu, Neelesh Sharma, Afshin Dowlati
Journal: Journal of Clinical Oncology (2013)

8114 Background: In EGFR-TKI responsive NSCLC, at progression only some tumor clones might carry resistance mechanisms. This provides a rationale for maintenance therapy with TKIs on progression and is supported by “tumor flares” noted in patients taken off of TKI therapy. Methods: Randomized, phase II study of chemotherapy (pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) in patients with progressive NSCLC following clinical benefit from erlotinib for &gt; 12 weeks. In Arm A Pemetrexed or Docetaxel were given at standard doses every 3 weeks to a maximum of 8 cycles. In Arm B chemotherapy was given with ERL at 150 mg oral daily dose on days 2-19 of each cycle. The primary endpoint was that continuation ERL in this patient population could extend PFS by 50%, from 3 to 4.5 months. The original enrollment goal was 39 pts per arm to allow 80% power to detect such a difference. Results: 46 patients were randomized (Arm A: 24; Arm B: 22). Early termination was due to slow enrollment. Patient characteristics were well balanced except for more females on Arm A (p=0.075). The median PFS on Arm A was 5.4 months and for Arm B was 4.6 months (p=0.569). The median overall survival (OS) on Arm A was 18.7 months and for Arm B 14.7 months (p=0.295). Multiple Cox regression analysis showed an impact of female gender on OS (HR 0.1) but not PFS (HR=0.49). EGFR status was available on 39/46 patients. 17 patients in Arm A and 14 Arm B were mutation positive. In analyzing mutation + only patients, no difference in PFS (p=0.332) or OS (p=0.346) was seen amongst the 2 groups. In the mutation + patients the 6 months PFS for Arm A was 39% and for Arm B was 32%. More toxicity was seen on Arm B as compared to Arm A. Irrespective of causal attribution, 1 grade 5 event occurred on Arm A as opposed to 2 events on Arm B. A total of 7 grade 3/4 events occurred on Arm A while 24 occurred on Arm B. Conclusions: No benefit was seen with the continuation of ERL in addition to chemotherapy as compared to chemotherapy alone in patients who had previously benefited from ERL but then showed progression. The combination arm showed significantly more toxicity. Clinical trial information: NCT00660816.
286P Efficacy, safety and pharmacokinetics (PK) of enzalutamide (ENZ) vs placebo (PL) in chemotherapy-naïve patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC): An Asian multinational study
Authors: D. Ye, H. Ahn, Y-S. Pu, W. Han, L-P. Xie, S-P. Huang, H-C. Wu, L. Ma, J. Qi, F. Zhou, G. Sun, L. Chen, B. Xue, S. Yamada, M. Saito, K. Suga, Y. Sun
Journal: Annals of Oncology (2016)
Safety and preliminary efficacy of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (aHCC): Interim analysis of the phase 1/2 CheckMate-040 study
Authors: I. Melero, B. Sangro, T. Yau, C. Hsu, M. Kudo, T. Crocenzi, T.-Y. Kim, S.-P. Choo, J. Trojan, T. Meyer, T.H. Welling, W. Yeo, A. Chopra, J. Anderson, C.l.a. De Cruz, L. Lang, J. Neely, A. El-Khoueiry
Journal: Annals of Oncology (2016)
Long-Lasting Effect of Allergen-Specific Sublingual Immunotherapy in a Murine Model of Japanese Cedar Pollinosis
Authors: Soichi Tofukuji, Kazufumi Katayama, Yoshiyuki Nakano, Satoru Ishida, Minako Tajiri, Junji Tsuchida, Makoto Kodama, Hiroki Tsuji, Kota Kawachi, Michitaka Shichijo, Hidekazu Tanaka
Journal: Journal of Allergy and Clinical Immunology (2017)
MyD88-Dependent Expansion of An Immature GR-1+CD11b+ Population From Donor Bone Marrow Reduces Early Mortality After Allogeneic Hematopoietic Stem Cell Transplantation,
Authors: Ji-Young Lim, Gyeongsin Park, Hyewon Youn, Eun-Young Choi, Dae-Chul Jeong, Chang-Ki Min
Journal: Blood (2011)
Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment
Authors: James L. Gulley, Ravi A. Madan, Russell Pachynski, Peter Mulders, Nadeem A. Sheikh, James Trager, Charles G. Drake
Journal: JNCI Journal of the National Cancer Institute (2016)

Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread). Immunotherapy-induced antigen spread has been shown in clinical studies. For example, in metastatic castration-resistant prostate cancer patients, sipuleucel-T induced early immune responses to the immunizing antigen (PA2024) and/or the target antigen (prostatic acid phosphatase). Thereafter, most patients developed increased antibody responses to numerous secondary proteins, several of which are expressed in prostate cancer with functional relevance in cancer. The ipilimumab-induced antibody profile in melanoma patients shows that antigen spread also occurs with immune checkpoint blockade. In contrast to chemotherapy, immunotherapy often does not result in short-term changes in conventional disease progression end points (eg, progression-free survival, tumor size), which may be explained, in part, by the time taken for antigen spread to occur. Thus, immune-related response criteria need to be identified to better monitor the effectiveness of immunotherapy. As immunotherapy antitumor effects take time to evolve, immunotherapy in patients with less advanced cancer may have greater clinical benefit vs those with more advanced disease. This concept is supported by prostate cancer clinical studies with sipuleucel-T, PSA-TRICOM, and ipilimumab. We discuss antigen spread with cancer immunotherapy and its implications for clinical outcomes.
Samuel L. Moschella, MD—An Exceptional Leader
Authors: June K. Robinson
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology 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 Dermatology journal
258P First-line chemotherapies with FOLFIRINOX or gemcitabine plus nab-paclitaxel for unresectable pancreatic ductal adenocarcinoma in Japanese daily clinical practice
Authors: M. Yano, T. Terashima, T. Yamashita, M. Miyazawa, H. Mizuno, Y. Nomura, None Omura, Y. Takata, N. Ooishi, H. Shugo, K. Yamada, H. Takabatake, H. Takatori, Y. Hodo, R. Nishino, T. Hayashi, E. Mizukoshi, S. Kaneko
Journal: Annals of Oncology (2016)
An Analysis of Potential Associations Between Delivery Mode and Dog-Keeping to Basophil FcER1 and Activation Marker Expression During Infancy
Authors: D. Orandi, S. Havstad, A. Sitarik, K. Bobbitt, K. Jones, A. Levin, N. Lukacs, S.V. Lynch, G. Wegienka, K. Woodcroft, D. Ownby, C. Johnson, E. Zoratti
Journal: Journal of Allergy and Clinical Immunology (2017)
NIMG-58. AUTOMATED APPROACH TO PREDICTING MALIGNANT TRANSFORMATIONS IN RECURRENT LOW-GRADE GLIOMAS USING EX VIVO SPECTROSCOPIC DATA
Authors: Stojan Maleschlijski, Adam Elkhaled, Llewellyn Jalbert, Marram P. Olson, Susan Chang, Joanna Phillips, Mitchel S. Berger, Sarah Nelson
Journal: Neuro-Oncology (2016)

To automatically classify recurrent low-grade gliomas (LGGs) that remain grade II versus those that have transformation to a higher grade (grade III or IV) by applying machine learning algorithms on ex vivo nuclear magnetic resonance (NMR) data, acquired from biopsy samples of LGG patients. Multivariate statistical models were used to identify regions in the spectra that were characteristic for each group and to obtain the metabolic signatures of both types of LGGs. Due to the high-dimensionality of spectroscopic data, we utilized orthogonal partial least squares discriminant analysis (OPLS-DA) to build the predictive model. This is a supervised learning algorithm well suited for the analysis of data where the number of observations is much smaller than the number of variables. The data comprised high-resolution magic angle spectroscopy (HRMAS) spectra of 112 image-guided tissue samples from 56 patients with recurrent LGG. Part of each sample was examined by a board-certified pathologist to evaluate histological grade and the remaining portion was analyzed using HRMAS. 43 samples (22 patients) originated from gliomas that remained grade II, 52 samples from 26 patients transforming to grade III and 19 samples from 8 patients transforming to grade IV. An OPLS-DA model (R2x=88%, R2y=94%, Q2=61% and root mean squared error of estimation RMSEE = 0.1) was trained and validated using leave-one-out cross-validation, resulting in mean specificity of 0.84 and sensitivity of 0.88. The peak regions containing the highest amount of discriminatory information for distinguishing between LGGs that transformed to a higher grade and those remaining grade II corresponded to glucose, myo-inositol, hypotaurine, choline, glycerophosphocholine, glutathione, 2-hydroxyglutarate, alanine, lactate and lipid. Metabolite signatures of tissue samples from lesions that remained grade II versus those that transformed to a higher grade included several features that can be measured non-invasively using in vivo H1 magnetic resonance spectroscopy.
MPTH-03. SCREENING BIOMARKERS IN GLIAL TUMORS TO IDENTIFY PREDICTORS OF SEIZURE ACTIVITY: A PROOF OF CONCEPT USING ISOCITRATE DEHYDROGENASE 1 (IDH-1) MUTATION STATUS
Authors: Margaret Johnson, Sarah Schmitt
Journal: Neuro-Oncology (2016)

This is a proof of concept to demonstrate whether screening pathological biomarkers, present in primary brain tumors, may be a useful strategy to identify epileptogenic tumor types. Using a single biomarker, isocitrate dehydrogenase gene (IDH-1), this study looks for an association between the presence or absence of IDH-1 and the risk of developing seizures. It has been established that tumor grade, location, necrosis, hemorrhage, and peri-tumoral tissue changes contribute to epileptogenesis. However, the precise mechanism is unknown. Seizures occur in up to 50% of patients with brain tumors. It is not understood why seizures occur more often in low-grade gliomas compared to high-grade gliomas, or metastases. This is a retrospective case control study. Using “PennSeek”, a tool to search unstructured medical documents at the Hospital of the University of Pennsylvania, 551 patients with “IDH-1” (positive or negative) were identified. Patients with non-glial pathology were excluded. Using ICD-9 codes, the patients with known IDH-1 status were divided into seizure versus seizure-free groups. Comparisons between these two groups were made with t-tests and Chi-square. The odds of having seizures in the IDH-1 positive group was 1.4 times that of the IDH1-1 negative group (95% CI 0.782-2.536, p=0.22). The most common pathology in IDH-1 positive patients who had seizure activity was oligodendroglioma (27.8%) compared to IDH-1 negative patients with seizures, whose predominant pathology was glioblastoma multiforme (54.3%). Without statistical significance, further evaluation to adjust for tumor location, necrosis, and hemorrhage was not pursued. There was an increased odds of seizure in IDH-1 positive patients. This was not a statistically significant finding. The same methodology may be applied to additional molecular markers: EGFR, P53, 1p19q co-deletion. Subsequent statistical analysis will provide better understanding of tumor epileptogenesis after adjusting for tumor location, grade, degree of necrosis, and hemorrhagic changes.
484O_PR Validation of the set of six adaptable prognosis prediction (SAP) models for cancer patients in palliative care settings: A sub analysis of the Japan-prognostic assessment tools validation (J-ProVal) study
Authors: Y. Uneno, M. Baba, M. Kanai, K. Taneishi, M. Nakatsui, Y. Okuno, M. Muto, T. Morita
Journal: Annals of Oncology (2016)
Phase II Study of Alemtuzumab Treatment in Patients with Pretreated T-Cell Lymphoma.
Authors: Pier Luigi Zinzani, Monica Tani, Vittorio Stefoni, Lapo Alinari, Enrica Marchi, Annalisa Gabriele, Gerardo Musuraca, Maria Paola Fina, Stefano Pileri, Michele Baccarani
Journal: Blood (2004)
14P Adipose tissue-derived stem cells provide an advantageous tumor microenvironment in gastric cancer
Authors: J. Kinoshita, S. Fushida, S. Harada, K. Oyama, T. Yamaguchi, A. Hirose, K. Okamoto, K. Nakamura, T. Miyashita, H. Tajima, H. Takamura, None Ninomiya, T. Ohta
Journal: Annals of Oncology (2016)