tbuckley/cabot-search huggingface dataset:
IMPS-08CONSTITUTIVE CELL INTRINSIC OVEREXPRESSION OF PD-L1 AND PD-L2 IN GLIOMA
Authors: Yujie Fu, Dale Kobayashi, Gavin Dunn
Journal: Neuro-Oncology (2015)

High-grade Gliomas (HGG) are the most common primary brain tumors and continue to carry a poor overall survival. Despite extensive molecular characterization, the “mutation-to-drug” paradigm has not been successfully applied to patients with glioblastoma as it has in other cancers. Due to the (a) success of checkpoint blockade immunotherapy, such as inhibition of the PD-1/PD-L1 pathway, in other tumor types and (b) the known immunologic comprise these patients exhibit, there has been tremendous enthusiasm regarding immune-based treatments in this setting. Although clinical trials incorporating the inhibition of the PD-1/PD-L1 pathway are ongoing, the biology underlying PD-L1 expression in glioma remains unclear. Moreover, there is a limited understanding of the underlying functional consequences of the expression of the related PD-1 ligand, PD-L2. To focus exclusively on the cell autonomous regulation of these ligands, we interrogated the Cancer Cell Line Encyclopedia, a Broad Institute/Novartis compendium of passaged cell lines independent of effects of the tumor microenvironment. We found that a subset of glioma cell lines harbor high constitutive PD-L1 and PD-L2 mRNA levels. Consistent with the mRNA levels, we showed that both PD-L1 and PD-L2 cell surface protein is overexpressed by flow cytometry. Two subsequent studies are ongoing. First, to identify the transcriptional basis of ligand upregulation, we have identified a suite of transcription factors using in silico analysis that harbor consensus binding sites in suspected promoter/enhancer regions and have modeled this using endogenous promoter/enhancer luciferase assays. Secondly, to determine the functional consequences of PD-L1 and/or PD-L2 overexpression in the anti-glioma immune response, we ectopically expressed these ligands in the GL-261 murine glioma cell line and tested their influence on T cell recognition of a model antigen. Together, these studies will clarify the regulation of the PD-L1/PD-L2 ligands and identify additional methods with which to decrease their immunosuppressive functions.
The case for immune‐based approaches in biliary tract carcinoma
Authors: Austin G. Duffy, Oxana V. Makarova‐Rusher, Tim F. Greten
Journal: Hepatology (2016)

Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune‐based approaches has yet to be seen. However, the etiological background of BTC—overlapping in almost every known causative or associated factor with inflammation—provides a strong clue that these approaches may have an impact in this group of diseases. This review covers what we currently know about the role of the immune system in the etiology of BTC, highlighting differences by subtype, and pointing to the therapeutic opportunities currently entering the clinic or about to do so. (H epatology 2016;64:1785‐1791)
The Ethical and Practical Challenges of Value-Based Cancer Care at the Patient’s Bedside
Authors: Daniel A. Goldstein
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology 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 Oncology journal
Plasma-Cell Myeloma
Authors: Elliott F. Osserman
Journal: New England Journal of Medicine (1959)

THE purpose of this article is primarily to review the more recent acquisitions to the knowledge and understanding of the pathophysiology of the plasma-cell dyscrasias. Several comprehensive studies of the clinical, radiographic, pathological and biochemical features of multiple myeloma have been published in the past thirty years.1 2 3 4 5 6 7 8 9 10 11 12 13 Major emphasis in this presentation, however, will be given to specific topics pertaining to plasma-cell neoplasia in which recent progress has been made.The "typical" case of multiple myeloma, if, indeed, such an entity exists, must now be considered as representing just one of several clinical patterns that may arise from a primary . . .
Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients
Authors: J. Gronwald, T. Byrski, T. Huzarski, R. Dent, V. Bielicka, D. Zuziak, R. Wisniowski, J. Lubinski, S. Narod
Journal: Journal of Clinical Oncology (2009)

502 Background: Neoadjuvant chemotherapy is administered to control disease, make surgical resection possible and increase the possibility of breast tissue conservation. A further advantage of neoadjuvant therapy is that it helps to assess chemo-sensitivity to a particular agent. Induction of a pathological complete response (pCR) is one of the primary goals of neoadjuvant therapy in order to achieve a better disease-free and overall survival. Experimental data suggest that BRCA1 related breast cancer may have increased sensitivity to platinum-based chemotherapy, but clinical data are limited. The aim of this study was to evaluate the frequency of complete pathologic response after neo-adjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. Methods: Twenty five women with breast cancer and a BRCA1 mutation with stage I, II, and III breast cancer between December 2006 and December 2008 were entered into this study. Patients were treated with cisplatin 75 mg/m 2 intravenously every three weeks for four cycles. After chemotherapy, patients underwent surgery and were assessed for pathologic response in both the breast and axillary lymph nodes. Complete pathologic response was defined as no residual invasive disease in both the breast and axilla, however ductal carcinoma in situ was allowed. Results: Twenty five patients were enrolled in the study. Thirteen patients had tumors of greater than two centimeters (52%) and seven patients had positive lymph nodes at diagnosis (28%). Twenty two patients completed four cycles of cisplatin (88%) and three patients completed two cycles (12%). Clinical complete response was observed in eighteen patients (72%). Pathologic complete response was observed in eighteen patients (72%). Conclusions: Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancers. Clinical trials are warranted to determine the optimum treatment for this subgroup of breast cancer patients. No significant financial relationships to disclose.
Vision of correction for classic homocystinuria
Authors: Dwight D. Koeberl
Journal: Journal of Clinical Investigation (2016)

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols. In this issue of the JCI, Bublil and colleagues demonstrate that enzyme replacement therapy (ERT) provides long-term amelioration of homocystinuria-associated phenotypes in CBS-deficient murine models. A PEGylated form of CBS provided long-term stability and, when used in conjunction with the methylation agent betaine, dramatically increased survival in mice fed a normal diet. The results of this study provide one of the first examples of ERT for a metabolic disorder and suggest that PEGylated CBS should be further explored for use in patients.
Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials
Authors: Boris Böll, Helen Goergen, Karolin Behringer, Paul J. Bröckelmann, Felicitas Hitz, Andrea Kerkhoff, Richard Greil, Bastian von Tresckow, Dennis A. Eichenauer, Carolin Bürkle, Sven Borchmann, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: Blood (2016)
More radiologists needed for improved cancer diagnosis, says royal college
Authors: Helen Mooney
Journal: BMJ (2016)

The Royal College of Radiologists has warned that a shortage of radiologists could hamper NHS England plans to provide fast tracked cancer diagnosis.

The national cancer strategy,1 launched by the National Cancer Transformation Board, unveiled plans for patients with suspected cancer to be diagnosed or have their cancer ruled out within four weeks of initial referral by a GP. From 2017 five areas will test the four week diagnosis standard.

NHS England will invest £15m ($22m; €19m) in a bid to provide “world class” cancer care by speeding up diagnosis, improving the experience of patients, and helping people living with …
A randomized phase II study of sunitinib versus dacarbazine in the treatment of patients with metastatic uveal melanoma.
Authors: Ernest Marshall, Sarah Coupland, Philippa Corrie, Bertil Damato, Sarah Danson, Lisa Dobson, T.R. Jeffry Evans, Andrew Goodman, Helen Kalirai, Sarah Jones, Satish Kumar, James M. G. Larkin, Paul Lorigan, Steve Nicholson, Christian Ottensmeier, Paul Silcocks, Neil Steven, Catrin Tudur-Smith, Paul D. Nathan
Journal: Journal of Clinical Oncology (2012)

TPS8605 Background: Metastatic uveal melanoma represents an orphan disease area with a median survival of less than 6 months. There is currently no effective systemic therapy for metastatic uveal melanoma and few clinical trials have been conducted. In the absence of phase III data, many patients in the UK continue to receive single agent dacarbazine or best supportive care outside of the context of clinical trials. Uveal melanoma is characterized by activation of the MAP kinase pathway via functionally activating mutations in Gnaq/11. Evidence also suggests that dysfunctional c-Kit signalling and angiogenesis may both play a role in disease progression and a small single-arm phase II trial recently reported preliminary activity using the multi-targeted receptor tyrosine kinase inhibitor, sunitinib (Tijani et al, ASCO 2010). Methods: The SUAVE trial aims to evaluate the Progression Free Survival (PFS) of good performance status patients treated with sunitinib or dacarbazine. Secondary objectives include: Overall Survival (OS), Overall Response Rate (ORR), safety, crossover PFS and response and biomarker analyses. SUAVE is a CR-UK-funded, open-label, randomised, phase II trial that will include 124 patients. Patients will be stratified according to their Helsinki Prognostic Index (ALP, largest diameter of largest metastasis, ECOG). Inclusion Criteria: good performance status patients with confirmed unresectable metastatic uveal melanoma, with at least one target lesion measurable by RECIST 1.1. Patients must not have received previous systemic therapy. At confirmed progression, good performance status patients may crossover to the other study treatment. The trial opened in Oct 2010 and as of 23 January 2012, had randomized 49 patients with at least 1 recruited from each of the 12 recruiting sites. There will be a total of 13 sites. Completion of the recruitment phase is expected within 36 months. Prospective tissue and blood sample collection for translational biomarker analyses is also ongoing. The SUAVE trial represents one of the largest randomised trials in this rare disease area (Clinical trial registry number: 2008-008794-55).
Predicting cardiovascular disease
Authors: Tim Holt
Journal: BMJ (2016)

An over-abundance of risk models offering few real benefits to patients

Emerging as a leading cause of death in the early 20th century and peaking in incidence in the 1960s, cardiovascular disease (CVD) remains a major global threat despite a progressively reducing incidence and case fatality for myocardial infarction and stroke. Since then, development of preventive interventions (pharmaceutical and lifestyle) led to a plethora of prediction models designed to identify those at risk, summarised in the linked systematic review by Damen and colleagues.1

Risk prediction for CVD began in 1948 when investigators started recruiting in Framingham, Massachusetts for their seminal cohort study,2 3 which resulted in risk equations combining the suspected risk factors. At this time there was a need to confirm and measure the relative contribution of these factors, as well as identify at risk individuals. Was smoking or blood pressure as important as raised cholesterol levels? How did these factors interact with each other, and with …
A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis
Authors: Erika Scholz, Anna Mestre‐Ferrer, Xavier Daura, Noel García‐Medel, Montserrat Carrascal, Eddie A. James, William W. Kwok, Francesc Canals, Iñaki Álvarez
Journal: Arthritis & Rheumatology (2016)

Objective To evaluate similarity of the peptide repertoires bound to HLA–DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides. Methods Peptide pools bound to HLA–DRB1*01:01, HLA–DRB1*04:01, and HLA–DRB1*10:01 (RA associated) and those bound to HLA–DRB1*15:01 (non–RA–associated) were purified and analyzed by liquid chromatography (LC) matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry (MS) and LC–ion‐trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA–DRB1 molecules and HLA–DRB5*01:01. Results A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions. Conclusion The degree of overlap between peptide repertoires associated with different HLA–DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu 4 and basic residues at the P8 position of the binding core.
Abstract P203: Restricting Sleep Duration Alters Resting and Postprandial Respiratory Quotient, but has Minimal Effects on Overall Energy Expenditure
Authors: Ari Shechter, Russell Rising, Jeanine Albu, Marie-Pierre St-Onge
Journal: Circulation (2013)

Introduction: Epidemiological evidence has demonstrated a link between short sleep and obesity. Clinical studies suggest a role of increased energy intake in this relationship, whereas the contributions of energy expenditure (EE) and substrate utilization are less clearly defined. Our aim was to investigate the effects of short sleep on EE and respiratory quotient (RQ) during sleep, basal conditions, and in response to a high-fat meal. Methods: Seven females (age and BMI: 27.4 ± 8.1 years and 26.2 ± 1.6 kg/m2, respectively) participated in a randomized, crossover study lasting 4 days. Participants were studied under two separate conditions: short (4 h/night; time in bed 0100-0500 h) and habitual (8 h/night; time in bed 2300-0700 h) sleep. Meals were served at 0800, 1200, and 1900 h, with a snack at 1600 h. Data included 24-h EE and sleep metabolic rate (SMR) from the metabolic chamber and fasting resting metabolic rate (RMR) and postprandial energy expenditure (PPEE) over a 6 h period after consumption of a high-fat breakfast on day 4. Results are expressed as mean ± SD. Results: Total 24-h EE was 1,907 ± 229 kcal and 1,830 ± 63 kcal for short and habitual sleep, respectively (p=0.084, paired t-test). Mean SMR was 0.967 ± 0.19 kcal/min throughout the 4-h sleep period and 0.895 ± 0.09 kcal/min throughout the 8-h sleep period (p=0.211, paired t-test). When we examined the 8-h period spanning the sleep episode during the habitual sleep phase, there was a significant sleep condition x time interaction for EE (p&lt;0.001). During the short sleep phase, this measurement included 4 h of sleep and 4 h of non-sleep time. Specifically, EE in the short sleep condition was significantly higher than in the habitual sleep condition mostly during non-sleep times: at 0000-0100, 0100-0200, 0500-0600, and 0600-0700 h, resulting in an increase of 0.21 ± 0.19 kcal/min (p=0.009) throughout the full 8-h period. RQ significantly declined across the 2300-0700 time period (p&lt;0.001), but did not differ between conditions. RMR after 3 nights of short vs. habitual sleep did not differ between conditions, whereas fasting RQ was significantly lower (p=0.026) after short vs. habitual sleep. Postprandial RQ and PPEE did not differ between conditions. The postprandial RQ peak was significantly reduced in short vs. habitual sleep (p=0.008, paired t-test). Conclusions: We demonstrate here that short sleep results in increased EE during nocturnal hours spent awake, but does not significantly alter SMR. Over the 24-h period, however, it results in a slight increase in EE, which was not significant with this sample size. These findings imply that the greater prevalence of obesity in individuals with short sleep observed in epidemiological studies is most likely attributable to greater food intake that is not offset by the small increase in EE associated with greater time spent awake.
Using Serum Free Light Chain (SFLC) Ratio and Serum Protein Electrophoresis (SPEP) As a Substitute For 24-Hour Urine Studies In Myeloma Patients
Authors: Ajay K. Nooka, Donald Harvey, Jonathan L. Kaufman, Amelia Langston, Dana Nickleach, Charise Gleason, Aocnp, Leonard T Heffner, Lawrence H. Boise, Sagar Lonial
Journal: Blood (2013)
Germline RBBP6 mutations in familial myeloproliferative neoplasms
Authors: Ashot S. Harutyunyan, Roberto Giambruno, Christian Krendl, Alexey Stukalov, Thorsten Klampfl, Tiina Berg, Doris Chen, Jelena D. Milosevic Feenstra, Roland Jäger, Bettina Gisslinger, Heinz Gisslinger, Elisa Rumi, Francesco Passamonti, Daniela Pietra, André C. Müller, Katja Parapatics, Florian P. Breitwieser, Richard Herrmann, Jacques Colinge, Keiryn L. Bennett, Giulio Superti-Furga, Mario Cazzola, Emma Hammond, Robert Kralovics
Journal: Blood (2015)
Expression Status of BCL-6 and Syndecan-1 Identifies Distinct Histogenetic Subtypes of Hodgkin's Disease
Authors: Antonino Carbone, Annunziata Gloghini, Gianluca Gaidano, Silvia Franceschi, Daniela Capello, Hans G. Drexler, Brunangelo Falini, Riccardo Dalla-Favera
Journal: Blood (1998)
MPTH-23DISTINCT MORPHOLOGY IN MOLECULAR SUBGROUPS OF GLIOBLASTOMA IN YOUNG PATIENTS
Authors: Julia Elisabeth Neumann, Andrey Korshunov, Christian Mawrin, Arend Koch, Armin Giese, Ulrich Schüller
Journal: Neuro-Oncology (2015)

Glioblastoma is a malignant brain tumor that occurs in all age groups and corresponds to WHO°IV. Based on genetics, global gene expression, and methylation patterns, glioblastoma may be categorized in different molecular subgroups. Among these subgroups “IDH” glioblastomas, which carry mutations within IDH1 or IDH2, as well as the “K27” and “G34” subgroups, which are characterized by distinct mutations within the H3F3A gene, can be clearly identified by sequencing methods and are particularly often found in younger patients below 30 years of age. We aimed to analyze the histomorphology of glioblastomas found in patients ≤30 years with the following assigned molecular subgroups: IDH (n = 12), H3F3A K27M (n = 21), H3F3A G34R (n = 12) or no IDH/H3F3A mutations (n = 24). Assessment of histomorphological characteristics was done blinded. IDH mutated cases displayed moderate cell densities and nuclear pleomorphism, showed an astroglial morphology and often harbored microcystic features or gemistocytic tumor cells. H3F3A K27M mutated cases more often showed necroses and displayed higher cell densities and pronounced nuclear pleomorphism. A fraction of these cases was additionally characterized by tumor giant cells. Glioblastoma cases carrying H3F3A G34R mutations predominantly displayed an undifferentiated/PNET-like morphology with densely packed cells and high nuclear pleomorphism. Tumor cell foci with epithelial appearance were specifically found in glioblastoma cases without IDH or H3F3A mutations. Moreover, a fraction of glioblastoma cases without IDH/H3F3A mutations exhibited tumor giant cells. Thus, molecular glioblastoma subgroups are characterized by distinct histomorphological features that can be detected by routine histology. Both IDH mutated cases and H3F3A G34R glioblastoma cases presented histomorphologically as a quite homogenous group. In contrast, H3F3A K27M cases and glioblastomas without IDH/H3F3A mutations displayed disparities of histomorphology, that might imply a more heterogeneous molecular picture. Our study underlines the diversity of glioblastoma and suggests that distinct morphological features reflect the underlying molecular characteristics.
Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study
Authors: Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Steven Coutre, John F Seymour, Talha Munir, Soham D Puvvada, Clemens-Martin Wendtner, Andrew W Roberts, Wojciech Jurczak, Stephen P Mulligan, Sebastian Böttcher, Mehrdad Mobasher, Ming Zhu, Monali Desai, Brenda Chyla, Maria Verdugo, Sari Heitner Enschede, Elisa Cerri, Rod Humerickhouse, Gary Gordon, Michael Hallek, William G Wierda
Journal: The Lancet Oncology (2016)
Is It Possible to Prevent ARDS?
Authors: John P. Reilly, Jason D. Christie
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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