tbuckley/cabot-search huggingface dataset:
Delays in the Publication of Important Clinical Trial Findings in Oncology
Authors: Lindor Qunaj, Raina H. Jain, Coral L. Atoria, Renee L. Gennarelli, Jennifer E. Miller, Peter B. Bach
Journal: JAMA Oncology (2018)

The complete and timely dissemination of clinical trial data is essential to all fields of medicine, with delayed or incomplete data release having potentially deleterious effects on both patient care and scientific inquiry. While prior analyses have noted a substantial lag in the reporting of final clinical study results, we sought to refine these observations through use of a novel starting point for the measurement of dissemination delays: the date of a corporate press release regarding a phase 3 study's results. To measure the length of time elapsed between when a sponsor had results of study findings they deemed important to announce, and when the medical community had access to them. Covering the years 2011 through 2016, we measured the delay from when 8 large pharmaceutical companies issued a press release announcing completed analyses of phase 3 clinical trials in oncology, and the public sharing of those results either on ClinicalTrials.gov or in a peer-reviewed biomedical journal as found via PubMed or Google Scholar. Press releases announcing regulatory steps and presentation schedules for conferences were excluded, as were those announcing results from preclinical trials, follow-up analyses, and studies of supportive care therapies or various modes of infusion for the same therapy. Time to public dissemination of clinical trial data. Of the 100 press releases in our sample, 70 (70%) reported positive results, but only 31 (31%) included the magnitude of study findings. Through the end of follow-up, 99 (99%) of press releases had an associated peer-reviewed publication, complete data posting to ClinicalTrials.gov, or both, with a median time to reporting of 300 days (95% CI, 263-348 days). Positive findings were reported more quickly than negative ones (median of 272; 95% CI, 211-318 days vs 407; 95% CI, 298-705 days; log-rank P < .001). Even for the most pressing study findings, median publication delays approach 1 year. As publication delays hinder research progress and advancements in clinical care, policies that enable early preprint release or public posting of completed data analysis should be pursued.
Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes
Authors: Jun Gi Rho, Hwa Seung Han, Ji Hye Han, Hansang Lee, Van Quy Nguyen, Wang Hee Lee, Seunglee Kwon, Sungeun Heo, Juhwan Yoon, Han Ho Shin, Eun-young Lee, Hoin Kang, Siyoung Yang, Eun Kyung Lee, Jae Hyung Park, Wook Kim
Journal: Journal of Controlled Release (2018)
Role and targeting of anaplastic lymphoma kinase in cancer
Authors: Carminia Maria Della Corte, Giuseppe Viscardi, Raimondo Di Liello, Morena Fasano, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello, Floriana Morgillo
Journal: Molecular Cancer (2018)

Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has demonstrated significant effectiveness in ALK-positive patients, in particular ALK-positive non- small cell lung cancer. Several mechanisms of resistance to these inhibitors have been described and new strategies are underway to overcome the limitations of current ALK inhibitors.
Toward a United States of Health: Implications of Understanding the US Burden of Disease
Authors: Howard K. Koh, Anand K. Parekh
Journal: JAMA (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 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
Absorption and Elimination of 15N After Administration of Isotopically Labelled Yeast Protein and Yeast Protein Hydrolysate to Adult Patients with Coeliac Disease
Authors: C. W. Crane, A. Neuberger
Journal: BMJ (1960)

Digestion in the normal human subject and the abnormalities in the enzymic hydrolysis and absorption of protein which are found in adult coeliac disease, as shown by investigations using '5N-labelled protein and protein hydrolysate, were discussed in two previous papers (Crane and Neuberger, 1960a, 1960b).This communication is concerned with the excretion of isotopic nitrogen in the urine, the origin of faecal nitrogen in normal man and in certain cases of steatorrhoea, and the possible effects on the general nutrition of the patient of increased nitrogen excretion in the faeces.Analyses of urine and faeces were carried out on the four patients investigated in the first paper of this series (Crane and Neuberger, 1960b), but we include the results of another patient who suffered from adult coeliac disease and who excreted an unusually large amount of nitrogen in his faeces.To this patient 15N- labelled glycine was administered and the effect on faecal nitrogen of varying the protein intake of the diet was examined. RESULTS Excretion of 15N in the UrineIn three experiments, A2, C3, and J, (Table I), in which normal subjects were fed yeast protein equivalent to about 0.9 mg. of "5N/kg.body weight, and allowed diets of their own choosing, the total 15N eliminated in the urine during the subsequent three days was remarkably constant.Values expressed as percentages of the amounts of 15N fed were 26.3, 26.6, and 27.4%.When labelled yeast protein hydrolysate was fed, equivalent to 0.83 mg."5N/kg.body weight in a similar experiment (C3), the excretion was 28.1%, but in a second experiment (A,) only 23.5% of the "5N was excreted in the urine in three days.However, this subject fasted over- night and for the first 12 hours of the experiment, and 250 ml. of blood was withdrawn; hence it is possible that this lower value reflects some degree of nitrogen retention.Excretion was higher when labelled yeast protein was fed to two subjects placed on measured diets, adequate in protein but deficient in calories, and values for three-day periods were 30.0 and 31.9% of the 15N fed (experiments Al and Cd).Compared with the findings in normal subjects, the 15N excreted in the urine after three days was much more variable when either whole-yeast protein or protein *Now at the Department of Medicine, Queen Elizabeth Hospital, Birmingham, 15.hydrolysate was fed to patients with coeliac disease.
Minoxidil for Endocrine Therapy–Induced Alopecia in Women With Breast Cancer—Saint Agatha’s Blessing?
Authors: Ralph M. Trüeb
Journal: JAMA Dermatology (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 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
A novel therapeutic to enhance the immunogenicity of breast cancer cells.
Authors: Priya Vishnubhotla, Amr Khaled, Anne Showalter, Jeremiah Oyer, Robert Igarshi, Alicja Copik, Annette Khalid
Journal: Journal of Clinical Oncology (2017)

119 Background: Breast cancer is a challenge for immunotherapy because of its inherent genetic heterogeneity and decreased immunogenicity. A possible solution is to generate dying breast cancer cells that operate like a vaccine to stimulate tumor-specific immunity. This is termed immunogenic cell death (ICD) and is characterized by a unique molecular signature, involving the release of molecules that attract and stimulate phagocytes and sensitize tumor cells to killing by natural killer (NK) cells. However, the current doses of drugs used to induce ICD may be too high to translate into clinically relevant regimens. Methods: Our group discovered a novel peptide, CT20p, that is effective at nanomolar concentrations and can be delivered to breast tumors using targeted nanoparticles. CT20p works by inhibiting a unique protein folding complex, called chaperonin-containing TCP-1 (CCT), which is highly expressed in cancer cells but not normal cells. Using triple negative breast cancer (TNBC) and normal cell lines as well as patient-derived tumor cells, we examined the biological consequences of CCT inhibition by CT20p in terms of the induction of endoplasmic reticulum (ER) stress, through the accumulation of unfolded proteins, and the release of the danger signals associate with ICD that could stimulate innate immunity. Results: Dying TNBC cells treated with CT20p displayed alterations in PERK, a mediator of the unfolded protein response (UPR), which resulted in the membrane translocation of calreticulin (Crt), an “eat me”’ signal and a key marker of ICD. CT20p-killed TNBC cells were more readily phagocytosed, and NK cells more effectively killed remaining cancer cells. In our experiments normal breast epithelial cells, macrophages or NK cells were unaffected by CT20p. Conclusions: Our study suggests that inhibition of CCT by CT20p generates dying cancer cells that stimulate innate immune responses, through the release of signals like Crt, to attract phagocytes and promote NK cell cytotoxicity. By enhancing the immunogenicity of breast cancer cells, CT20p could increase responsiveness to to checkpoint inhibitors or cellular immunotherapy, hence providing more complete protection from breast cancer recurrence and metastasis.
Long-term follow-up of DNA engineered bi-shRNA furin GMCSF plasmid/autologous tumor induced immune response in patients with advanced solid tumors (phase I trial).
Authors: John J. Nemunaitis, Minal A. Barve, Anton Melnyk, Gladice Wallraven, Luisa Manning, Neil N. Senzer
Journal: Journal of Clinical Oncology (2017)

110 Background: Previously we described safety and evidence of activity to Vigil Ò (FANG Ò ) and identified relationship of survival advantage to ELISPOT “+” Vigil treated patients (Senzer N et al. Long Term Follow Up: Phase I Trial of “bi-shRNA furin/GMCSF DNA/Autologous Tumor Cell” Immunotherapy (FANG) in Advanced Cancer. J Vaccines Vaccine 2013; 4: 209. doi: 10.4172/2157-7560.1000209). We have updated survival and long-term ELISPOT assessment of this same group of patients. Methods: A non-randomized phase 1 trial of patient treated with Vigil immunotherapy (n=39) compared to a similar matched comparator (MC) group not treated with Vigil (n=35). Results: Trial results suggest survival benefit without evidence of Vigil related toxicity (no ≥ grade 3). γ-IFN ELISPOT served as a biomarker for response and shows correlation with survival. 22/30 evaluable Vigil-treated patients showed ELISPOT conversion (73%) from negative to positive (threshold of ≥10 spots from baseline) during treatment. Durable evidence of γIFN-secreting circulating cytotoxic T cells was observed (up to 30months from treatment start), suggesting induction of memory T effector cells. Survival correlation demonstrated significant benefit of ELISPOT “+” Vigil treated patients (median OS of 784 days, 26.1 months) compared to ELISPOT “-“ patients (median OS of 353 days, 11.77 moths), and supports immune-related survival benefit compared to MC (median OS of 122 days, 4 months), (Table). Conclusions: Vigil immunotherapy induces a significant immune response. Detailed analysis of the immune effector population phenotype is underway to determine optimal correlation with survival. Clinical trial information: NCT01061840. [Table: see text]
128O Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes
Authors: D. Planchard, M. Boyer, J-S. Lee, A. Dechaphunkul, P. Cheema, T. Takahashi, A. Todd, A. McKeown, Y. Rukazenkov, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation
Authors: Reina Nagase, Daichi Inoue, Alessandro Pastore, Takeshi Fujino, Hsin-An Hou, Norimasa Yamasaki, Susumu Goyama, Makoto Saika, Akinori Kanai, Yasuyuki Sera, Sayuri Horikawa, Yasunori Ota, Shuhei Asada, Yasutaka Hayashi, Kimihito Cojin Kawabata, Reina Takeda, Hwei-Fang Tien, Hiroaki Honda, Omar Abdel-Wahab, Toshio Kitamura
Journal: The Journal of Experimental Medicine (2018)

Additional sex combs like 1 (ASXL1) is frequently mutated in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP). Although loss of ASXL1 promotes hematopoietic transformation, there is growing evidence that ASXL1 mutations might confer an alteration of function. In this study, we identify that physiological expression of a C-terminal truncated Asxl1 mutant in vivo using conditional knock-in (KI) results in myeloid skewing, age-dependent anemia, thrombocytosis, and morphological dysplasia. Although expression of mutant Asxl1 altered the functions of hematopoietic stem cells (HSCs), it maintained their survival in competitive transplantation assays and increased susceptibility to leukemic transformation by co-occurring RUNX1 mutation or viral insertional mutagenesis. KI mice displayed substantial reductions in H3K4me3 and H2AK119Ub without significant reductions in H3K27me3, distinct from the effects of Asxl1 loss. Chromatin immunoprecipitation followed by next-generation sequencing analysis demonstrated opposing effects of wild-type and mutant Asxl1 on H3K4me3. These findings reveal that ASXL1 mutations confer HSCs with an altered epigenome and increase susceptibility for leukemic transformation, presenting a novel model for CHIP.
Lupus—Crying Wolf
Authors: Sarah Azarchi, Arielle R. Nagler
Journal: JAMA Dermatology (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 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
Four-Dimensional Imaging of T Cells in Kidney Transplant Rejection
Authors: Andrew D. Hughes, Fadi G. Lakkis, Martin H. Oberbarnscheidt
Journal: Journal of the American Society of Nephrology (2018)

Kidney transplantation is the treatment of choice for ESRD but is complicated by the response of the recipient’s immune system to nonself histocompatibility antigens on the graft, resulting in rejection. Multiphoton intravital microscopy, referred to as four-dimensional imaging because it records dynamic events in three-dimensional tissue volumes, has emerged as a powerful tool to study immunologic processes in living animals. Here, we will review advances in understanding the complex mechanisms of T cell–mediated rejection made possible by four-dimensional imaging of mouse renal allografts. We will summarize recent data showing that activated (effector) T cell migration to the graft is driven by cognate antigen presented by dendritic cells that surround and penetrate peritubular capillaries, and that T cell–dendritic cell interactions persist in the graft over time, maintaining the immune response in the tissue.
Generation and characterization of antitumor infiltrating lymphocytes from patients with breast cancer for adoptive cell transfer therapy.
Authors: Juhua Zhou, Yin Zhong, Zhongjun Hou, Jianzhong Zhang, Yanmin Li, Senxiang Yan
Journal: Journal of Clinical Oncology (2017)

145 Background: Clinical trials have shown that adoptive cell transfer therapy is a promising method for cancer treatment. In the current study, we aim to generate and characterize anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer for adoptive cell transfer therapy. Methods: In vitro culture method was used to generate anti-tumor, tumor-infiltrating lymphocytes from patients with breast cancer. FACS analysis, ELISA, and Elispot assay were used to characterize tumor-infiltrating lymphocytes. Autologous anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer were used in adoptive cell transfer therapy. Results: FACS analysis indicated that tumor-infiltrating lymphocytes were present in the tumor tissues, but not detectable in the normal breast tissues from patients with breast cancer. Tumor-infiltrating lymphocytes could be generated in vitro from fresh tumor specimens of patients with breast cancer. Both CD4 T cells and CD8 T cells were detected in tumor-infiltrating lymphocytes. Autologous tumor cells could also generate in vitro from fresh tumor tissue samples of patients with breast cancer. Among 22 samples screened, 6 samples (25%) of tumor-infiltrating lymphocytes are tumor-reactive. Anti-tumor, tumor-infiltrating lymphocytes could recognize autologous tumor cells and allogenic tumor cells. After a large scale T cell expansion, anti-tumor reactivity was maintained in tumor-infiltrating lymphocytes. All of tumor-infiltrating lymphocytes were NK cells in some samples from patients with breast cancer, and these NK cells could recognize autologous tumor cells and a panel of allogenic tumor cells. T cell cloning assay demonstrated that some of the tumor-reactive, tumor-infiltrating lymphocytes were CD4 T cells. Conclusions: The results suggest that anti-tumor, tumor-infiltrating lymphocytes may be generated from patients with breast cancer, which may be used in clinical applications of adoptive cell transfer therapy for patients with breast cancer. The clinical trial of adoptive cell transfer therapy using autologous anti-tumor tumor-infiltrating lymphocytes for patients with breast is under way.
Traumatic brain injury raises dementia risk, large study suggests
Authors: Ingrid Torjesen
Journal: BMJ (2018)

People who have sustained a traumatic brain injury have a higher risk of developing dementia and Alzheimer’s disease, a nationwide population cohort study suggests.

Published in the Lancet Psychiatry ,1 the study is one of the first to have a sufficient sample size and follow-up time to assess the effects of traumatic brain injury.

It includes data on 2 794 852 people living in Denmark on 1 January 1995 who were aged at least 50 at some point in the follow-up period (1999-2013). Registries were used to identify people who had sustained a …
A new approach for immuno-oncology biomarker discovery: High-plex, spatial protein profiling based on NanoString digital quantification.
Authors: David Lee, Yan Liang, Chris Merritt, Fiona Pakiam, Giang Ong, Shaobu Weng, Dwayne Dunaway, Jaemyeong Jung, Sarah Warren, Scott Crowder, Joseph M Beechem, Wendy Winckler
Journal: Journal of Clinical Oncology (2017)

27 Background: The immune response to cancer is shaped by the abundance and localization of immune cell populations, their activation status, and expression of immunomodulatory factors. To detect proteins at high multiplex with spatial resolution, NanoString optical barcoding technology was used to digitally profile protein expression in formalin fixed paraffin embedded (FFPE) samples and compared to traditional IHC. Methods: NanoString has enabled digital profiling of immuno-oncology protein targets, including immune cell markers and checkpoint proteins. Protein detection is enabled via primary antibodies (Abs) which are attached via a UV cleavable linker to DNA indexing oligos. FFPE samples are stained with a multiplex cocktail of labeled Abs, then DNA oligos are released by UV light exposure. Liberated oligos are then hybridized to optical barcodes for quantitation on a NanoString instrument. This technique enables quantitative, multiplex protein detection over 5 logs of dynamic range. IHC and NanoString spatial protein profiling were performed on alternating sections from blocks of tonsil, melanoma, and colorectal cancer. Sections were fluorescently labeled with panCK, Ki67, and Syto-83 to visualize morphology, and regions of interest (ROI) were selected for profiling using up to 30 oligo-tagged Abs. Results: NanoString counts strongly correlated with quantification of CD3, CD4, CD8, PanCK, Ki67, PD-1, and PD-L1 derived from IHC. To explore limits of detection, ROIs of 1, 2, 4, or 8 cells were profiled. Digital counts were detected above background at the single cell level and linearly correlated with cell count. Furthermore, quantification with two cell lineage markers and double positive cells were demonstrated using a 30-plex Ab cocktail. Conclusions: Multiplex, digital protein profiling with spatial resolution will enable deep characterization of immune responses in tumors. Additionally, single cell profiling enables inter-cellular characterization of variations in immune response. The strong correlation of NanoString data to IHC indicates the feasibility to spatially profile multiple key proteins with minimal consumption of patient tissue.