tbuckley/cabot-search huggingface dataset:
Curatopes Melanoma: A Database of Predicted T-cell Epitopes from Overly Expressed Proteins in Metastatic Cutaneous Melanoma
Authors: Christopher Lischer, Martin Eberhardt, Tanushree Jaitly, Cornelia Schinzel, Niels Schaft, Jan Dörrie, Gerold Schuler, Julio Vera
Journal: Cancer Research (2019)

Therapeutic anticancer vaccination has been adapted as an immunotherapy in several solid tumors. However, the selection of promising candidates from the total quantity of possible epitopes poses a challenge to clinicians and bioinformaticians alike, and very few epitopes have been tested in experimental or clinical settings to validate their efficacy. Here, we present a comprehensive database of predicted nonmutated peptide epitopes derived from genes that are overly expressed in a group of 32 melanoma biopsies compared with healthy tissues and that were filtered against expression in a curated list of survival-critical tissues. We hypothesize that these "self-tolerant" epitopes have two desirable properties: they do not depend on mutations, being immediately applicable to a large patient collective, and they potentially cause fewer autoimmune reactions. To support epitope selection, we provide an aggregated score of expected therapeutic efficiency as a shortlist mechanism. The database has applications in facilitating epitope selection and trial design and is freely accessible at https://www.curatopes.com. SIGNIFICANCE: A database is presented that predicts and scores antitumor T-cell epitopes, with a focus on tolerability and avoidance of severe autoimmunity, offering a supplementary epitope set for further investigation in immunotherapy.
SP0093 Junctional adhesion molecule-2 (jam-2) is localised at intercellular junctions and plays a role in lymphocyte transmigration
Authors: B Imhof, CA Johnson-Léger, M Aurrand-Lions, C Wong
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> We identified a novel Junctional Adhesion Molecule by a selective RNA display method. The protein was named JAM-2 based on its 30–40% homology to JAM and VE-JAM. The three JAMs define a novel subset of immunoglobulin superfamily molecules which will be referred to as JAM-1 (JAM), JAM-2 and JAM-3 (VE-JAM). JAM-2 is highly expressed by HEVs and lymphatic endothelial cells in lymphoid organs, suggesting that it may play a role in lymphocyte recirculation. The role of JAM-2 in inter-endothelial junctions has been addressed using endothelial cells over-expressing JAM-2 protein. These cells have an increased ability to sustain lymphocyte transmigration in agreement with the pattern of expression found <i>in vivo</i>. Transfected cells are also more permeable to FITC-dextran. Furthermore, an antibody directed against the extracellular domain of JAM-2 is able to partially block the transmigration. Our findings suggest that JAM-2 may facilitate lymphocyte extravasation across HEVs by rendering the inter-endothelial junctions more leaky. The role of JAM-2 in inflammatory processes will be discussed. <h3>Reference</h3> Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem. 2001;276:2733–41
Post-progression survival (PPS) according to treatment line, type, and time in phase III trials in advanced colorectal cancer (ACC).
Authors: Marc E. Buyse, Everardo D. Saad, Alastair Matheson
Journal: Journal of Clinical Oncology (2012)

3557 Background: Since post-progression therapy influences overall survival (OS), PPS is of interest as a determinant of OS. We quantified the relationship between several median times to event in ACC: progression-free survival (PFS), PPS and OS. We looked for factors with an impact on these times. Methods: We searched PubMed for phase III trials published between January 1998 and December 2010 in 12 leading journals. PPS is the difference between median OS and median PFS or time to tumor progression. The statistics of interest (median times [PFS, OS and PPS] and the ratio of PPS/OS) were compared using t-tests. Results: We retrieved 70 trials that yielded 71 comparisons and 156 arms (one trial was factorial) involving 38,504 patients. Trials from the period 2005-10 enrolled more patients than trials from the period 1998-2004 (medians of 246 vs 174 per arm; P=.026). PPS could be calculated for 60 trials and 135 arms (Table). Treatment type did not have an impact on any statistic. Treatment line had a significant impact on all times and on the ratio of PPS/OS, although the difference on the latter statistic was small. Treatment period had a significant impact on all times but not on the ratio of PPS/OS. Conclusions: None of the factors examined have a major impact on the ratio of PPS/OS. This suggests that in ACC, gains in PFS are translated into proportional gains in OS, one of the conditions required for PFS to be considered a surrogate for OS. [Table: see text]
Inhibition of Lactate Dehydrogenase (LDH-A) potentiates the activity of NQO1 (NAD(P)H:Quinone oxidoreductase-1) by increasing cellular NADH levels.
Authors: Milene Volpato, Julien Ablain, Roger Phillips
Journal: Cancer Research (2008)

4358  NQO1 is a cytosolic flavoprotein which catalyses the two electron reduction of substrates (particularly quinones) using NADH and/or NADPH as electron donors. The switch from oxidative phosphorylation to glycolysis as the major source of energy production in tumour cells (the Warburg effect) has potential implications for the activity of NQO1. NAD+ is generated following the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) and this is used to drive the conversion of glyceraldehyde 3 phosphate to 1,3 bisphosphoglycerate. As a result, NADH/NAD+ ratios are low suggesting that the activity of NQO1 in tumours could be hindered. As NQO1 has been implicated in both the detoxification and bioreductive activation of quinone based compounds, strategies designed to enhance the levels of NADH in tumour cells may have significant toxicological or therapeutic implications. In cell free assays, the ability of purified NQO1 to reduce menadione were strongly dependent upon NADH concentration. Protein and mRNA expression of LDH-A were determined in a panel of cell lines and cells with low (MCF7) and high (H460) LDH-A expression were selected. Sodium Oxamate, a known competitive inhibitor of LDH-A with respect to pyruvate, displayed a Ki of 1.86 mM against purified rabbit muscle LDH-A. Exposure of MCF-7 and H460 cells to a range of oxamate concentrations (20 µM to 10 mM) for 2 hours was well tolerated with minimal cell kill (
Current Landscape of Treatments for Wolfram Syndrome
Authors: Damien Abreu, Fumihiko Urano
Journal: Trends in Pharmacological Sciences (2019)

Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum disorder.
Introduction of Combined Chemotherapies Plus Rituximab (R) Has Improved Outcome of Previously Untreated and Relapsed Follicular Lymphoma (FL) Patients (pts).
Authors: Stefano Sacchi, Samantha Pozzi, Luigi Marcheselli, Alessia Bari, Stefano Luminari, Massimo Federico, Francesco Angrilli, Marco Lombardo, Chiara Broglia, Giovanni Quarta, Maura Brugiatelli
Journal: Blood (2006)
Neuroblastoma inhibit dendritic cell maturation by expressing phosphatidylserine on the cell surface
Authors: Joel Shilyansky, Xiao Chen, Kara Doffek, Sonia L. Sugg
Journal: Cancer Research (2006)

3140  The mechanisms by which neuroblastoma (NB), a childhood malignancy with poor prognosis, inhibits DC maturation are not well understood. We made the novel observation that NB cells express phosphatidylserine (PS) on the cell surface. PS is an anionic phosphalipid restricted to the cytoplasmic side of the plasma membrane bilayer in most live cells and externalized early in the process of apoptosis. The effect of exposure to NB-PS on DC maturation and function was examined. DCs, generated from donor PBMCs in the presence of GM-CSF and IL-4, were exposed to NB cells and treated with TNF∈± or LPS to induce maturation. DC maturation was assessed using flow cytometry and cytokine production was assayed using ELISA. DCs were used to stimulate allogeneic T cells and proliferation was detected using [3H]-Thymidine incorporation and CFSE profiling. NB cells inhibited expression of MHCII, CD80, CD86 and CD83, production of IL-12, TNF-alpha and IL-6 and ability to activate allogeneic T cells by DCs. Separating DCs and NB cells using transwells prevented the inhibitory effect on maturation. Similarly blocking PS on the surface of NB cells using Annexin-V (AnV), a protein that binds PS specifically, attenuated the inhibitory effect on DC maturation. Blocking IL-10, TGF-beta, VEGF or the ganglioside GD2 did not prevent the inhibitory effect of NB cells on DC maturation. In summary, PS, on the surface of NB cells, inhibits DC maturation and immunostimulatory function. Expressing PS on the cell surface may be a novel mechanism for modulating the immune response and evading destruction by NB.
Abstract #751: Predictive value of a gene-signature identified in 3D cultures in breast cancer treated with Docetaxel.
Authors: Katherine Martin, Mina Bissell, Marcia Fournier
Journal: Cancer Research (2009)

Background and objective: The identification of predictive markers for response of breast cancers to therapy is an intensive area of research. We hypothesized that using a physiologically relevant model would identify a signature composed of key, biologically relevant genes and therefore likely to predict therapeutic efficacy across independent datasets. Candidate predictive genes were selected using a well-defined three dimensional (3D) cell culture model of non-malignant human cells that can reacquire the ability to form acini-like structures presenting a lumen, basal polarity and cell cycle arrest in laminin-rich extracellular matrix 3D cultures. These acinar structures replicate many of the characteristics of luminal cell differentiation in the mammary gland. The gene expression profiles of acini formation were determined as a function of time in culture. Gene expression that was modulated during growth arrest and acini formation in 3D cultures (3D-signature) was compared and validated against gene expression measured in cancer and then correlated to patient outcome. Methods and results: We investigated the predictive value of the 3D-signature for response to therapy. We used a published microarray dataset of 24 breast tumors treated with Docetaxel with annotated clinical information (Chang JC et al. Lancet, 2003 362:340-1). The microarray dataset used tissue samples taken before treatment and patients were subsequently found to be resistant to or sensitive to docetaxel treatment. The predictive value of therapeutic sensitivity was analyzed using the 3D-signature. Probesets for 17 of 22 3D-signature genes were present on the HG-U95AV2 microarrays. 2D hierarchical clustering was used to separate patients into 2 groups. The 3D signature accurately predicted drug sensitivity (p=0.0014 Fischer\#8217;s exact test). Conclusions: Validation of the predictive power of the 3D-signature could lead the development of a clinical test for docetaxel sensitivity. These studies together are a proof of principle of the application of physiologically relevant models such as 3D-cultures to predict clinical response to therapy.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 751.
An automated virtual screening system for identification of novel therapeutics.
Authors: John J. Irwin, Brian K. Shoichet
Journal: Cancer Research (2004)

Notwithstanding well-known algorithmic weaknesses, molecular docking screens have had important successes in recent years, and are now the most practical technique to leverage structure for ligand discovery. Unfortunately, barriers to entry have largely restricted the techniques to experts and their collaborators. Docking databases are expensive to acquire, require considerable manipulation, and the software is byzantine. There are many other pitfalls for the unwary, for example in the preparation of the protein binding site and the choice of dozens of parameters. This has diminished the impact of the technique and limited the sorts of problems to which it can be applied. To address this situation we are building tools and databases that will bring docking to a broad audience, in the spirit of BLAST, and allow its application to new questions. This talk will describe the development of and experience with an early prototype of an automated web-based docking system and its components. We will focus on specific examples of ligand discovery using molecular docking, illustrating some of the strengths and weaknesses of an automated web-based facility.
SAT0196 Stereologic measurement of inflammatory synovial membrane volume on mr images
Authors: A Savnik, HS Thomsen, JR Nyengaard, H Bliddal
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Manual outlining of the synovial membrane on MR images in inflammatory joint diseases is too time consuming for clinical use. <h3>Objectives</h3> The purpose was to introduce a less time-consuming stereologic method for measuring synovial volume by MRI in inflammatory joint diseases. <h3>Methods</h3> Post-contrast 3-D T1-weighted turbo gradient MR images of the finger (metacarpophalangeal and interphalangeal) joints (14 joints) were acquired from 11 patients with rheumatoid arthritis (n = 8) and reactive arthritis (n = 3). Manually outlined volume was taken as a gold standard and compared with stereologic volume estimation on transverse 1 mm thick slices. <h3>Results</h3> The total volume of 154 finger joints was estimated. A significant correlation between manual and stereologic estimations of synovial volumes was found (Spearman rho = 0.71, P = 0.002). 95% limits of agreement were ± 5–6 ml (14 finger joints per patient). The time used for volume determination in a patient varied from 1–2.5 h by manual outlining and from 0.5–1 h by stereologic determination. <h3>Conclusion</h3> Stereologic volume estimation can provide measures of synovial volumes comparable to the manual outlining method and is less time-consuming. Stereologic volume estimation seems to be a clinically useful method, especially if it is integrated in the MR unit?s workstation.
Neither Pause nor Gaze at What Is Passing
Authors: Risa Denenberg
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
Abstract #4913: Role of Rac1 GTPase in the epithelial-mesenchymal transition and the \#8220;stemness\#8221; of human lung adenocarcinoma cells
Authors: Shailaja Akunuru, Yi Zheng
Journal: Cancer Research (2009)

The cancer stem cell theory predicts that a small population of cancer cells possesses unique self-renewal activity and is the source of cells with varying expansion and differentiation capabilities in tumors. Recently, side population (SP) cells, along with cells expressing a number of cell surface markers including CD133, have been identified in lung, brain, blood, colon, or breast cancers to represent an enriched cancer stem cell population [1, 2]. An interesting proposal has been put forward that epithelial-mesenchymal transition (EMT), a process known to be critical in several developmental programs and in cancer cell metastasis and invasion, promotes the characteristics of \#8220;stemness\#8221; in normal or cancer cells [3]. The latter study raises the possibility that targeting EMT may be beneficial in not only inhibiting cancer cell invasion but also blocking the cancer stem cell generation and tumorigenesis. Given the implicated role of Rac1 GTPase in tumor cell proliferation and in morphological transition associated with EMT, we have investigated the hypothesis that Rac1 is a critical mediator of cancer cell EMT and tumor initiating activity in human lung adenocarcinoma cells. We have found that (1) SP cells isolated from lung cancer cell lines are enriched for tumor initiating cells and possess increased colony-forming, migratory, and invasive activities; (2) the SP cells represent a distinct population from the CD133+ cells, with both containing an enriched tumor-initiating activity; (3) TGF\#946;1 induced EMT in A549 cells results in a complete disappearance, rather than an increase, of SP cells, and the effect of TGF\#946;1 on EMT and the SP population of cells is reversible; (4) Rac1 is significantly activated when the cells undergo EMT, and pharmacological or shRNA inhibition of Rac1 dampens the SP cell growth, migration, and invasion. We are in the process of sorting out the complex relationship amongst cancer stem cell activities, SP and CD133+ cell populations, EMT, and Rac1 activity, and are stringently testing in vitro cell models and in vivo mouse xenograft models. References: 1.%9Ho, M.M., et al., Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res, 2007. 67(10): p. 4827-33. 2.%9Eramo, A., et al., Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ, 2008. 15(3): p. 504-14. 3.%9Mani, S.A., et al., The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008. 133(4): p. 704-15.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4913.
The meaning of race in science and in society
Authors: Harold Freeman
Journal: Cancer Research (2007)

LE02-01  Race is perhaps  single most defining issue in  history of American society. This nation9s unique history overwhelmingly provides  background on which  concept of race is based. Popular conceptualizations of race date back several centuries and in particular are rooted in 19th and 20th century scientific thought. The presumption that visible traits produced  measure of all other internal traits in an individual or population has pervaded our national history and is a basis on which we see, value and behave toward one another.  American classifications of race came out of this history in which people were categorized by external visible traits (skin color, hair type, facial features etc) and treated differently. Furthermore, science has been a major force in establishing and reinforcing such  classifications. Past and current United States Census categories reflect this history of classification by race. For example,  Office of Management of  Budget (OMB) Directive number 15 sets forth  and ethnic categories used in  census. This Directive goes on to say that the collection of information and use of these categories is required for  that meets  National Institutes of Health definition of clinical research At  same time  OMB states that racial and ethnic categories are social-political constructs and should not be interpreted as being scientific in nature.  >Against this background, both American society and science operate. To illustrate, in both science and society, race is often used as a proxy for poverty, class, education, discriminatory experiences and certain behaviors, among other factors. But recent studies based on an understanding of  human genome, population genetics and physical anthropology now lead to  conclusion that  categories as used in  US census are not biologically determined.  >We conclude that at this time in American society, race does exist from a social perspective. To  extent that people are racially categorized and treated differently, race is real.  >However, races as used in  US census do not exist as biological categories from a scientific perspective.  >Given  fact that human populations do differ, and that race is not  basis for those variations, scientists face  challenge of elucidating how populations really differ.  >Moreover, in concert with our increasing scientific understanding of populations there is a need to augment our understanding of  social, economic and cultural determinants of population differences.  >In conclusion, everything we know about population genetics,  human genome and physical anthropology makes it clear that  classification has no scientific basis. Race is a social construct determined primarily by how one group perceives, values and behaves toward another group.  >The power of science can be used to eliminate false perceptions of  meaning of race and could prove pivotal in moving our society toward  justice and reconciliation. Physicians and scientists must be leaders in promoting this evolution in understanding.