tbuckley/cabot-search huggingface dataset:
Abstract 12: A novel Hsp90 machine inhibitor combining chemotherapy and immunotherapy
Authors: Ahmed Chadli, Nada Eisa, Vincent Crowley, Sumin Lu, Yasmeen Jilani, Hasan Korkaya, Brian Blagg
Journal: Cancer Research (2019)

Abstract Molecular chaperones are guardians of the proteome and of cellular homeostasis. Dysregulation in the function of the Hsp90 chaperoning machine in particular has been implicated in metabolic, oncological, neurodegenerative, and cardiovascular diseases. Targeting Hsp90 has been shown to have a combinatorial impact on dysfunctional circuitries that underlie human cancers. Thus, several inhibitors targeting the N-terminal ATP-binding pocket of Hsp90 are undergoing clinical trials as anticancer agents. They inactivate the ATPase activity of the chaperone, causing proteasomal degradation of its “client” oncogenic proteins. Although these inhibitors provided a proof-of-principal that Hsp90 is a valuable therapeutic target, they exhibit modest activity in the clinic, in part because they concomitantly induce a heat shock response (HSR), which turns on pro-survival pathways. Consequently, new mechanisms to inhibit the Hsp90 chaperone machine that do not induce the heat shock response are needed. To address this, we have developed a unique high throughput screen (HTS) based on the progesterone receptor (PR) and the five purified chaperones required for folding steroid receptors, i.e., Hsp90, Hsp70, Hsp40, Hsp70/Hsp90 organizing protein (Hop), and p23. During our preliminary screening of natural products, we discovered that the compound AD07 kills cancer cells through inhibition of the Hsp90 machine without a significant induction of HSR. In addition, AD07 induces a powerful T cell-mediated immune response, resulting in highly efficient tumor killing in a syngeneic mouse model and long-term memory against the primary tumor. At the molecular level, AD07 reduces the protein levels of two key mediators of tumor-induced immune tolerance: programmed cell death ligand-1 (PDL-1) and indolamine 2,3 dioxygenase (IDO). We therefore propose that AD07 is a promising anti-tumor agent targeting the Hsp90 machine through a novel mechanism of action involving cancer cell toxicity, which increases its immunogenicity, and modulation of the tumor microenvironment to reduce immunotolerance. Citation Format: Ahmed Chadli, Nada Eisa, Vincent Crowley, Sumin Lu, Yasmeen Jilani, Hasan Korkaya, Brian Blagg. A novel Hsp90 machine inhibitor combining chemotherapy and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 12.
Validation of the EORTC QLQ-C30 Summary Score in patients with hematological malignancies.
Authors: Francesco Cottone, Fabio Efficace, Kathrin Sommer, Giovanni Caocci, Paola Fazi, Marco Vignetti, Johannes M. Giesinger
Journal: Journal of Clinical Oncology (2019)

e18551 Background: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a widely used questionnaire, which assesses 15 patients’ self-reported health domains, including physical and emotional functioning and key cancer symptoms. As this poses analytical challenges such as multiple testing, a single QLQ-C30 summary score (SS) was recently validated in solid tumors. In this work, we investigated its validity in patients with hematological malignancies. Methods: According to the published scoring algorithm, the SS is the mean of 13 QLQ-C30 scale scores, a higher SS rating reflecting a better health status. We performed univariate linear regression analysis to investigate the ability of the SS to discriminate between patients groups differing on known characteristics, i.e. ECOG performance status (0-1 vs. 2-3), comorbidity (yes vs. no), red blood cells transfusion dependency (TD, yes vs. no, MDS patients only), age (≤ 60 vs. &gt; 60 years) and sex. We used linear mixed models to assess responsiveness of the SS to change, comparing baseline versus post-induction scores. For all analyses, we compared the SS performances to those of each original QLQ-C30 scale by Cohen's effect size (ES). Results: Analyses were based on pooled data from 2,134 patients diagnosed with myelodysplastic syndromes (MDS, n = 1,031), chronic myeloid leukemia (n = 382), acute myeloid (AML, n = 477) and promyelocytic leukemia (n = 244). Overall, 56.4% patients were male and the mean age was 51.5 years. Comparing groups by ECOG and comorbidity, SS outperformed 12 of the QLQ-C30 scales for ECOG (ES = 0.66) and 11 scales for comorbidity (ES = 0.17). With patients grouped by age (ES = 0.17) and sex (ES = 0.25), SS outperformed 13 and 12 scales respectively. For TD the SS (ES = 0.21) showed better discrimination than eight QLQ-C30 scales. When comparing baseline versus post-induction scores (AML patients), SS was more sensitive to change (ES = 0.41) than 10 of QLQ-C30 scales. Conclusions: Our findings provide support for the validity of the EORTC QLQ-C30 summary score as an endpoint in patients with hematological malignancies, when previous knowledge does not allow for domain-specific hypotheses.
Abstract 19019: Loss of Cardiac Myosin Binding Protein-C Leads to Ineffective Contraction and Relaxation Kinetics Which are Reinstated by Reintroducing the Phosphorylated Protein
Authors: Paola C Rosas, Yang Liu, Carl Tong
Journal: Circulation (2017)

Cardiac myosin binding protein-C (cMyBP-C), a heart muscle thick filament protein, can regulate cross-bridge attach/detachment process by its phosphorylation status. Moreover, ablation of cMyBP-C l...
Progression of Interstitial Lung Disease in Systemic Sclerosis: The Importance of Pneumoproteins Krebs von den Lungen 6 and CCL18
Authors: Elizabeth R. Volkmann, Donald P. Tashkin, Masataka Kuwana, Ning Li, Michael D. Roth, Julio Charles, Faye N. Hant, Galina S. Bogatkevich, Tanjina Akter, Grace Kim, Jonathan Goldin, Dinesh Khanna, Philip J. Clements, Daniel E. Furst, Robert M. Elashoff, Richard M. Silver, Shervin Assassi, A. C. Theodore, R. W. Simms, E. Kissin, F. Y. Cheong, V. D. Steen, C. A. Read, C. Fridley, M. Zulmatashvili, R. A. Wise, F. M. Wigley, L. Hummers, G. Leatherman, R. M. Silver, C. Strange, F. N. Hant, J. Ham, K. Gibson, D. Rosson, D. P. Tashkin, R. M. Elashoff, M. D. Roth, P. J. Clements, D. Furst, E. R. Volkmann, S. Kafaja, E. Kleerup, D. Elashoff, J. Goldin, E. Ariola, G. Marlis, J. Mason‐Berry, P. Saffold, M. Rodriguez, L. Guzman, J. Brook, J. Golden, M. K. Connolly, A. Eller, D. Leong, M. Lalosh, J. Obata, S. Volkov, D. Schraufnagel, S. Arami, D. Franklin, J. Varga, J. Dematte, M. Hinchcliff, C. DeLuca, H. Donnelly, C. Marlin, D. J. Riley, V. M. Hsu, D. A. McCloskey, K. Phillips, D. Khanna, F. J. Martinez, E. Schiopu, J. Konkle, M. Mayes, B. Patel, S. Assassi, F. Tan, A. Fischer, J. Swigris, R. Meehan, K. Brown, T. Warren, M. Morrison, M. B. Scholand, T. Frecht, P. Carey, M. Villegas, J. Molitor, P. Carlson
Journal: Arthritis & Rheumatology (2019)

To investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).Patients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.Baseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).In a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.
Navigating the Choppy Waters Between Public Safety and Humane Care of the Prisoner-Patient: The Role of the Ethics Consultant
Authors: Laurel J. Lyckholm, Laura A. Shinkunas
Journal: The American Journal of Bioethics (2019)

As illustrated by the case of Mr. J, the care of the prisoner as patient, or “prisoner-patient,” is often complicated by tension between the goals of incarceration, which in this case focus on inca...
Physicians’ Responsibilities in Shared Decision Making for Lung Cancer Screening—Reply
Authors: James S. Goodwin, Shawn Nishi, Yong-Fang Kuo
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract 15906: Apabetalone Downregulates Factors That Promote Vascular Calcification and Contribute to Cardiovascular Events
Authors: Dean Gilham, Laura Tsujikawa, Sylwia Wasiak, Christopher Halliday, Stephanie Stotz, Kamyar Kalantar-Zadeh, Richard Robson, Ravi Jahagirdar, Jan Johansson, Mike Sweeney, Norman Wong, Ewelina Kulikowski
Journal: Circulation (2017)

Introduction: Apabetalone, an orally active BET inhibitor, reduced incidence of major adverse cardiac events (MACE) in patients with CVD and improved eGFR in a subpopulation with chronic kidney dis...
Abstract 4166: Hereditary cancer syndromes in Guatemalan population
Authors: Claudia L. Carranza, Mariela Guerra, Claudia Osorio, Vanessa Zamora, Vivian Herrera, Jose Gil, Luis Alvarez
Journal: Cancer Research (2019)

Abstract BACKGROUND The majority of cancer are sporadic, only around 5 % are considered hereditary. Although it is a low percentage, the study of these cancers are of vital importance, since they require a special clinical monitoring and management. These kind of cancers are caused by the presence of an inherited gene mutation, which increase the risk of developing a tumor. The mutations associated with these tumors are germline mutations, this means that are present in all the patient's cells, including the egg cell an sperm; this is the reason why this type of cancer can transmit to the future generations. There are many syndromes that increase the risk of hereditary cancer development, the most frequent syndromes are: Familial Breast and Ovarian cancer (BRCA1 and BRCA2 gene mutations), Lynch syndrome (MSH2, MLH1, MSH6 and PMS2 mutations), Li-Fraumeni syndrome (TP53 gene mutations) and Familial adenomatous polyposis (APC gene mutations). The aim of this study is to screen the most common hereditary cancer syndromes in Guatemalan population. METHODS We analyzed 199 blood samples of patients with different types of tumors. We extracted DNA from the samples and then analyzed the gene mutations by next generation sequencing. RESULTS AND DISCUSSION We have included in the present study, 93 cases with Familial Breast cancer and 106 with another type of tumors. Of all cases, we have found 17 cases with hereditary cancer syndromes (8%). The most frequent is the Breast and Ovarian hereditary syndrome caused by BRCA1 and BRCA2 (12 patients). The other hereditary cancer syndromes are shown in Table 1. The detection of this germline mutations, have a large impact in the familial cases, because these patients and their families could be monitored and evaluated more frequently. This is the first report of these syndromes in our population. CONCLUSION We reported 6 different syndromes and 17 cases, related to hereditary cancer risk and predisposition in Guatemalan population. Frequency of hereditary cancer syndromesSYNDROMENUMBER OF PATIENTSCANCER TYPEAGESEXGENE MUTATIONBreast and ovarian hereditary syndrome7Breast cancer29-48FBRCA1Breast and ovarian hereditary syndrome5Breast cancer29-71FBRCA2Lynch syndrome1Breast cancer80FMSH6Li-Fraumeni syndrome1Breast cancer58FTP53Breast hereditary cancer1Breast cancer57FCDH1Peutz-Jeghers syndrome1Pancreatic cancer15FSTK11Familial adenomatous polyposis1Colorectal cancer13MAPC Citation Format: Claudia L. Carranza, Mariela Guerra, Claudia Osorio, Vanessa Zamora, Vivian Herrera, Jose Gil, Luis Alvarez. Hereditary cancer syndromes in Guatemalan population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4166.
Abstract 2767: Expression of defensin-associated genes may be correlated with lymph node metastasis of early stage tongue cancer
Authors: Doh Young Lee
Journal: Cancer Research (2019)

Abstract OBJECTIVES: Appropriate patient selection for elective neck dissection in N0 tongue cancer has been controversial, while there has been no genetic consideration so far. We aimed to analyze genetic difference between early and late cervical lymph node metastasis in oral tongue cancer patients using the Seoul National University Hospital (SNUH) cancer cohort and cancer genome atlas (TCGA) data, and to suggest genetic background for choosing eligible patient for elective neck dissection. METHODS: A total of 35 cases with RNAseq in SNUH cancer cohort with tongue cancer were also enrolled in this study. To investigate gene expression in early cervical lymph node metastasis, genomic data of following 2 groups was compared; 1) N0 group: T1/2 and N0, 2) N+ group: T1/2 and N+. Differentially expressed genes (DEGs) were extracted using R and limma package in bioconductor program. Gene ontology and pathway enrichment analysis were performed using DAVID online tool. Immune cell infiltration was analyzed using CIBERSORT online program. Additionally, 70 cases with matched RNAseq data of primary tumor and clinical TCGA data were analyzed to validate the role of DEGs. RESULTS: N0 and N+ groups showed no difference in age, gender, size and thickness of tumor, and nearest resection margin. In addition, there was no significant difference in 22 types of immune cell infiltration. A total of 51 DEGs were identified, and 14 genes were significantly upregulated and 37 genes were significantly downregulated (p&amp;lt;0.01, fold-change &amp;gt;2). Significant genes were PLA2G4D, NELL2, PCOLCE2, PI3, and PLA2G3. On KEGG pathway analysis, calcium, muscle contraction, and arachidonic acid metabolism-related pathway was significantly correlated. The most significant difference was found in 6 genes as follows; DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, FAM25A.DEFB which was the most significantly difference in expression was associated with ‘antibiotic’, ‘antimicrobial’, ‘beta defensing type’, defense reponse to bacterium’, and ‘defensin’. In TCGA data, DEFB4A and DEFB103B were more highly expressed in N0 group than N+ group, although it did not attain significant significance. CONCLUSIONS: Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer. Considering that defensin can be detected in saliva, simple saliva test for prediction of metastasis can be developed in the future. Note: This abstract was not presented at the meeting. Citation Format: Doh Young Lee. Expression of defensin-associated genes may be correlated with lymph node metastasis of early stage tongue cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2767.
An epidemiologic study of lifestyle of cancer patients presenting at National Hospital and Cancer Research Centre Pvt. Ltd., Jawalakhel, Nepal.
Authors: Rashmey Pun, Sandhya Chapagain Acharya, Madan Kumar Piya
Journal: Journal of Clinical Oncology (2013)

e12572 Background: Nepal being one of the economically challenged developing countries has been lagging behind in all healthcare facilities. Cancer is now emerging as a major Non-communicable (NCD) disease accounting for 9% of all NCDs. Lack of preventive measures, screening and awareness programme is hindrance in the early diagnosis. Hence, we aimed to study the epidemiological variables of various cancers so that risk factors can be identified. Methods: A Prospective, observational, cross sectional study was conducted from July 2012 to December 2012 for a period of six months. All patients with histological diagnosis of cancer attending the National Hospital and Cancer Research Centre were enrolled. A Questionnaire was formed in English and patients were asked to answer the questionnaire. Results: Out of 142 patients diagnosed with cancer, 22 different types of cancer were noticed and the most common was lung cancer in both sex with 28% incidence followed by breast 18%, gynecological cancer 15%, colorectal 9%, hepatobillary 9%, gastrointestinal 8%, lymphoma 6%, Head and neck 4%. Out of them, 61% were females and 39% were males and 96% of patient were married. The most common age group at diagnosis was 41-60 years and comprised of 42% of total. About 37% of the patient earned their living by agriculture. About 44% of the patient has annual income of over USD 2500. The most common ethnic group with cancer was identified as Newar with 48% prevalence of cancer. About 36% of the patients were illiterate, 20% are literate. Total of 51% of the patient were smoker, 19% are taking alcohol till recently and 27% consume alcohol occasionally. Only 9% of the patient are vegetarian and the 91% non-vegetarian group mostly eat red meat. Significant number (64%) of the patient is consuming the commercial, canned food. Very few patients are aware of exercise (22%) and meditation (11%). Conclusions: This is a single institution study and with lots of limitation. However, this can be used to find risk factors associated with our ethnic and cultural variation and thus a multicentric study is advisable to formulate National level preventive and screening programme.
Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin
Authors: Maria Júlia Correia Lima Nepomuceno Araújo, Igor Denizarde Bacelar Marques, Fabiana Giorgetti Graciolli, Luzia Fukuhara, Luciene Machado dos Reis, Melani Custódio, Vanda Jorgetti, Rosilene Mota Elias, Elias David-Neto, Rosa M.A. Moysés
Journal: Kidney International (2019)
Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation
Authors: Giorgia Battipaglia, Myriam Labopin, Nicolaus Kröger, Antonin Vitek, Boris Afanasyev, Inken Hilgendorf, Johannes Schetelig, Arnold Ganser, Didier Blaise, Maija Itälä-Remes, Jakob R. Passweg, Francesca Bonifazi, Jurgen Finke, Annalisa Ruggeri, Arnon Nagler, Mohamad Mohty
Journal: Blood (2019)
Abstract 3940: Acute total body ionizing radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat
Authors: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, Steven Mog, V Ashutosh Rao
Journal: Cancer Research (2019)

Abstract Radiation-induced heart disease presents a significant challenge in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the Wistar-Kyoto and spontaneously hypertensive rat model, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body irradiation at two, four, and fifty-two weeks. We further examined irreversible oxidative protein carbonylation in the heart immediately following irradiation. Both males and females sustained reduced growth and anemic conditions over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected by elevated IL-6 serum levels in males at four weeks. Serum cardiac troponin T and I analyses revealed indications of cardiomyopathy at earlier time points while more variability in the troponin levels was observed at one year. Echocardiography at two weeks following 5.0Gy treatment revealed hypertrophy and decrease in cardiac output in the short term, but significant differences were not observed at the one-year timepoint. Cardiac output was decreased in both males and females after two weeks, and statistically significant in females. Following irradiation, the heart tissue showed an increase in total protein carbonylation accompanied by DNA damage indicated by an increase in γ-H2AX. We present novel findings of several proteins that showed a marked change in carbonylation profile including those of mitochondrial origin. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals. Citation Format: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, Steven Mog, V Ashutosh Rao. Acute total body ionizing radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3940.
Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations
Authors: Giovanni Orsolini, Irene Elizabeth Maria Bultink, Giovanni Adami, Angelo Fassio, Ombretta Viapiana, Alessandro Giollo, Davide Gatti, Maurizio Rossini
Journal: Annals of the Rheumatic Diseases (2019)

We read with great interest the 2019 update of the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) published by Fanourakis et al .1 We would like to compliment the authors with their efforts to formulate updated recommendations which will help to improve the management of patients with SLE. They focus on different domains and introduce new concepts on disease treatment and management. The recommendations also deal with comorbidities, a huge problem in SLE patients, providing recommendations for the management of the antiphospholipid syndrome, infections and cardiovascular disease risk assessment and management. As the authors underline, the management of comorbidities in SLE is a key target to reduce damage accrual, disability and mortality. However, we believe that also osteoporosis and fractures should be considered as a …