tbuckley/cabot-search huggingface dataset:
Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion
Authors: Hsin-Yu Chen, Peder E.Z. Larson, Robert A. Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W. Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B. Vigneron
Journal: Cancer Research (2017)

Abstract New magnetic resonance (MR) molecular imaging techniques offer the potential for noninvasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a three-dimensional dynamic dual-agent hyperpolarized 13C magnetic resonance spectroscopic imaging approach with 13C-pyruvate and 13C-urea to investigate differences in perfusion and metabolism between low- and high-grade tumors in the transgenic adenocarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade. kPL values were relatively higher for high-grade TRAMP tumors. The increase in kPL flux correlated significantly with higher lactate dehydrogenase activity and mRNA expression of Ldha, Mct1, and Mct4 as well as with more proliferative disease. There was a significant reduction in perfusion in high-grade tumors that associated with increased hypoxia and mRNA expression of Hif1α and Vegf and increased ktrans, attributed to increased blood vessel permeability. In 90% of the high-grade TRAMP tumors, a mismatch in perfusion and metabolism measurements was observed, with low perfusion being associated with increased kPL. This perfusion-metabolism mismatch was also associated with metastasis. The molecular imaging approach we developed could be translated to investigate these imaging biomarkers for their diagnostic and prognostic power in future prostate cancer clinical trials. Cancer Res; 77(12); 3207–16. ©2017 AACR.
Janus Kinase 2 Regulates Transcription Factor EB Expression and Autophagy Completion in Glomerular Podocytes
Authors: Tamadher A. Alghamdi, Syamantak Majumder, Karina Thieme, Sri N. Batchu, Kathryn E. White, Youan Liu, Angela S. Brijmohan, Bridgit B. Bowskill, Suzanne L. Advani, Minna Woo, Andrew Advani
Journal: Journal of the American Society of Nephrology (2017)

The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion. In cultured podocytes, knockdown of JAK2 similarly impaired autophagy and led to downregulation in the expression of lysosomal genes and decreased activity of the lysosomal enzyme, cathepsin D. Because transcription factor EB (TFEB) has recently emerged as a master regulator of autophagosome-lysosome function, controlling the expression of several of the genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated by JAK2. In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter activity, expression, and nuclear localization. In silico analysis and chromatin immunoprecipitation assays revealed that the downstream mediator of JAK2 signaling STAT1 binds to the TFEB promoter. Finally, overexpression of TFEB in JAK2-deficient podocytes reversed lysosomal dysfunction and restored albumin permselectivity. Collectively, these observations highlight the homeostatic actions of JAK2 in podocytes and the importance of TFEB to autophagosome-lysosome function in these cells. These results also raise the possibility that therapeutically modulating TFEB activity may improve podocyte health in glomerular disease.
What are NCI-designated cancer centers using for breast cancer HER2 testing?
Authors: Kalliopi P. Siziopikou, Christine B. Weldon, Julia R. Trosman, William John Gradishar, Julian C. Schink
Journal: Journal of Clinical Oncology (2013)

626 Background: After 15 years of HER2 testing in breast cancer, various testing methods are used in practice. Studies comparing methods are published but no consensus exists on which method is best. Our study provides a benchmark on the use of breast HER2 testing methods in leading U.S. cancer centers. Methods: We conducted an IRB-approved web survey of 58 NCI cancer centers (pathologists and oncologists) providing adult breast cancer care. The survey included 14 questions on breast HER2 testing methods, and reflex and retest practices. We analyzed results using simple frequencies and Fisher's exact test. Results: We achieved a response rate of 98% (57/58 sites). In this cohort, 42% (24/57) of sites conduct HER2 testing for breast cancer using an IHC method with reflex to FISH. Of these, all sites reflex IHC 2+ results and 54% (13/24) automatically reflex IHC results beyond 2+ (see table, results are not mutually exclusive). Concurrent primary FISH and IHC testing is conducted at 32% (18/57) of sites; FISH only testing at 18% (10/57); concurrent primary SISH and IHC testing at 5% (3/57); concurrent primary CISH and IHC testing at 2% (1/57), and CISH only testing at 2% (1/57) of sites. The choice of testing protocol had no correlation with the size of institution, metro vs rural location, NCCN membership, or whether the site acts as a reference lab. However, sites where oncologists always or often request a specific test method were more likely (75%, 21/28) to use FISH as a primary method vs as a reflex method (38%, 9/24), p=.0108. Repeat HER2 testing on surgical tumor samples, after the core biopsy, was reported by 47% of sites (27/57); retesting of relapsed patients by 63% (36/57); and retesting for progressive metastatic disease by 56% (32/57). Conclusions: For HER2 breast biomarker testing, concurrent FISH and IHC testing and expanded reflex testing, beyond IHC 2+ results, have become a common practice at the NCI designated cancer centers. [Table: see text]
Immunotherapy in genitourinary malignancies
Authors: Kathan Mehta, Keyur Patel, Rahul A. Parikh
Journal: Journal of Hematology & Oncology (2017)

Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
Effect of age on the pharmacokinetics of busulfan (Bu): An alliance study.
Authors: Jan Hendrik Beumer, Lionel D. Lewis, Kouros Owzar, Chen Jiang, Julianne L. Holleran, Susan M. Christner, William G. Blum, Steven M Devine, Jonathan E. Kolitz, Charles A. Linker, Richard A. Larson, Mark J. Ratain, Merrill J. Egorin
Journal: Journal of Clinical Oncology (2012)

2533 Background: Older acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients (pts) have been excluded from myeloablative regimens including agents such as busulfan because of the potential for non-disease related morbidity and mortality. Busulfan, often used as part of myeloablative regimens, is cleared in part by glutathione–S-transferase and CYP3A4. We hypothesized that busulfan clearance (BuCL) in the elderly (&gt; 60 years) would be reduced compared to that in young patients (&lt; 60 years), thus potentially explaining differences in tolerability. Methods: AML and MDS pts in three CALGB bone marrow transplant studies across a wide age range (17-74) were treated with a conditioning regimen using IV busulfan, dosed at 12.8 mg/m 2 in CALGB studies 10503 and 19808 and 6.4 mg/m 2 in CALGB 100103. Blood samples were collected for determination of busulfan plasma pharmacokinetics (PK). Plasma busulfan was quantitated by LC-MS. BuCL was determined using non-compartmental modeling, and normalized to actual (ABW), ideal (IBW) and corrected (CBW) body weight (kg). Differences between age groups were examined using the Wilcoxon rank sum test. Results: A total of 185 pts were accrued and signed consent, of which 174 provided useable PK data. Twenty-nine pts ≥60 years old (median age 66.3) had a significantly higher mean BuCL vs those &lt; 60 years old (median age 49.8); BuCL 263 vs 186 mL/min, p=0.0002; BuCL/ABW 3.22 vs 2.34 mL/min/kg, p=0.0001; BuCL/IBW 3.63 vs 2.91 mL/min/kg, p=0.0035; BuCL/CBW 3.50 vs 2.70 mL/min/kg, p=0.0005. Inter-patient variability in clearance (CV%) was up to 47% in the elderly and up to 48% in young patients. Phenytoin use, a potential confounder, did not affect BuCL, regardless of weight normalization (p=0.74). Conclusions: Contrary to our hypothesis, BuCL is significantly higher in pts ≥60 years old compared to younger patients and does not explain the previously reported increase in Bu toxicity observed in the elderly.
A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism
Authors: Yu Meng, Jennifer A. Wiseman, Yuliya Nemtsova, Dirk F. Moore, Jenieve Guevarra, Kenneth Reuhl, William A. Banks, Richard Daneman, David E. Sleat, Peter Lobel
Journal: Molecular Therapy (2017)
Validation of Painreportit Neuropathic Pain Scale in African American Adults with Sickle Cell Disease
Authors: Keesha Roach, Robert E Molokie, Zaijie Jim Wang, Mariam O Ezenwa, David Shuey, Jesus Carrasco, Veronica Angulo, Judith Schlaeger, Marie L Suarez, Yingwei Yao, Diana J Wilkie
Journal: Blood (2016)
TCTAP A-004 Early Clinical Outcomes Following “Off-” Versus “On-label” Indications of Bioresorbable Vascular Scaffolds for the Treatment of 1505 Patients with Coronary Artery Disease: Results from the Prospective “Registro Absorb Italiano” (RAI Registry)
Authors: Alfonso Ielasi, Bernardo Cortese, Elisabetta Moscarella, Bruno Loi, Giuseppe Tarantini, Francesco Pisano, Alessandro Durante, Giampaolo Pasquetto, Alessandro Colombo, Gabriele Tumminello, Luciano Moretti, Paolo Calabrò, Pietro Mazzarotto, Attilio Varricchio, Maurizio Tespili, Giuseppe Steffenino
Journal: Journal of the American College of Cardiology (2017)
PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells
Authors: Xiong Ni, Qingxiao Song, Kaniel Cassady, Ruishu Deng, Hua Jin, Mingfeng Zhang, Haidong Dong, Stephen Forman, Paul J. Martin, Yuan-Zhong Chen, Jianmin Wang, Defu Zeng
Journal: Journal of Clinical Investigation (2017)

Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models. Depletion of donor CD4+ T cells increased serum IFN-γ but reduced IL-2 concentrations, leading to upregulation of PD-L1 expression by recipient tissues and donor CD8+ T cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+ T cells cause anergy, exhaustion, and apoptosis, thereby preventing GVHD. In lymphoid tissues, the interactions of PD-L1 with CD80 augment CD8+ T cell expansion without increasing anergy, exhaustion, or apoptosis, resulting in strong GVL effects. These results indicate that the outcome of PD-L1-mediated signaling in CD8+ T cells depends on the presence or absence of CD4+ T cells, the nature of the interacting receptor expressed by CD8+ T cells, and the tissue environment in which the signaling occurs.
TCTAP C-155 Extensive Iatrogenic Dissection of Right Coronary Artery Due to Guiding Catheter Associated with Radial Spasm During Percutaneous Coronary Intervention of Distal Right Coronary Artery- A Nightmare in the CathLab
Authors: Vipin Mughilassery Thomachan
Journal: Journal of the American College of Cardiology (2017)
FDG PET/CT Findings of Nodular Sclerosis–Subtype Classic Hodgkin Lymphoma Presented as Mediastinal Nodal Lesions at Onset But as Predominant Osseous Disease at Relapse
Authors: Kun Zheng, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

Nodular sclerosis-subtype classic Hodgkin lymphoma in general manifests as bulky mediastinal lymphadenopathy but very rarely involves bones. We report FDG PET/CT findings of a 19-year-old man with pathology-proven, nodular sclerosis-type classic Hodgkin lymphoma. His initial FDG PET/CT scan at the diagnosis showed only hypermetabolic lymphadenopathy in the mediastinum. However, the FDG PET/CT acquired when the disease recurred 20 months later showed predominant osseous disease without additional nodal lesions outside the mediastinum.
Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
Authors: E. Saâda-Bouzid, C. Defaucheux, A. Karabajakian, V.P. Coloma, V. Servois, X. Paoletti, C. Even, J. Fayette, J. Guigay, D. Loirat, F. Peyrade, M. Alt, J. Gal, C. Le Tourneau
Journal: Annals of Oncology (2017)
Abstract #3630: Characterization of recombinant fusion toxin GrB/YCG targeting LHR expressing cancer cells
Authors: Isao Kanatani, Xinjian Lin, Gerald Manorek, Xiaoqin Yuan, Lawrence Cheung, Michael Rosenblum, Stephen Howell
Journal: Cancer Research (2009)

Human chorionic gonadotropin (hCG) and luteinizing hormone normally affect only gonadal tissues where they play an essential role in reproductive function, but receptors for these hormones (luteinizing hormone receptor, LHR) are found in reasonable abundance on human ovarian, breast, endometrial and prostate carcinomas. While efforts have been made to use a 15 amino acid peptide derived from the \#946; subunit of hCG to target a membrane-disrupting lytic peptide to this receptor, these molecules are immunogenic, relatively impotent and have a very short half-lives in the systemic circulation. No immunotoxins that target LHR have entered clinical trials. In this study, we have constructed a fusion toxin consisting of the human pro-apoptotic serine protease Granzyme B (GrB) and the \#945; and \#946; chains of hCG yoked together. The GrB fused to the single-chain yoked hCG (YCG) was expressed in soluble form in Sf9 insect cells and purified by nickel-NTA metal affinity chromatography. Western blotting confirmed incorporation of both YCG and GrB proteins into the construct. The GrB/YCG displayed intact serine protease activity at the same level as human recombinant GrB, which was determined in a continuous colorimetric assay using N-\#945;-t-butoxycarbonyl-L-alanyl-L-alanyl-L-aspartyl-thiobenzyl ester (BAADT). An in vitro hormone binding assay revealed that the GrB/YCG molecule also retained the ability to bind to the LHR receptor with an affinity similar to that of native hCG. To establish a biological system for testing the potency and selectivity of GrB/YCG, we used the high-level LHR-expressing mouse Leydig tumor cells and created a LHR-knockdown subline by infection with an shRNAi-expressing lentivirus, designated here as LD-Clone 5.3, in which LHR messenger RNA levels measured by RT-PCR were reduced to 10% relative to that in the parental Leydig cells. The decrease in mRNA was accompanied by 93% loss of LHR binding capacity to 125I-hCG. In a parallel cytotoxicity study, GrB did not produce differential kill of the parental and LHR-knockdown cells whereas GrB/YCG was more effective at killing LHR-expressing Leydig cells compared to LHR-knockdown cells. In conclusion, we successfully made a fusion toxin that functions as both GrB serine protease and a high affinity ligand for the LHR. These results strongly suggested that LHR is a good therapeutic target and provided the basis for our current efforts to develop hCG-based toxins for targeted therapy of reproductive system tumors which over-express the receptor. This research was funded by the Clayton Medical Research Foundation.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3630.
March for Science
Authors: Caroline Weinberg
Journal: Annals of Internal Medicine (2017)

Ideas and Opinions20 June 2017March for ScienceCaroline Weinberg, MD, MPHCaroline Weinberg, MD, MPHFrom the March for Science, New York, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-0889 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail On the morning of 24 January 2017, during an infuriating conversation with a friend about the new U.S. administration's silencing of scientists, I idly floated the idea of organizing a March for Science. Less than 10 hours later, I found myself at the center of a global movement focused on defending the role of science in society and policy.The defense of science is necessary. Our society faces a dramatic flood of challenges, including restrictions on communicating scientific work and promises of budget cuts at major scientific institutions. These actions threaten the future of science and the fundamental research that ...References1. Briske DD. Translational science partnerships: key to environmental stewardship. BioScience. 2012;62:449-50. CrossrefGoogle Scholar2. Brewer PR, Ley BL. Whose science do you believe? Explaining trust in sources of scientific communication about the environment. Science Communication. 2012;35:115-137. CrossrefGoogle Scholar3. Bleich S, Blendon R, Adams A. Trust in scientific experts on obesity: implications for awareness and behavior change. Obesity (Silver Spring). 2007;15:2145-56. [PMID: 17712134] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the March for Science, New York, New York.Disclosures: The author has disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0889.Corresponding Author: Caroline Weinberg, MD, March for Science, 60 East 42nd Street Suite 565, New York, NY 10076; e-mail, [email protected]com.Author Contributions: Analysis and interpretation of the data: C. Weinberg.Drafting of the article: C. Weinberg.Final approval of the article: C. Weinberg.This article was published at Annals.org on 18 April 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAlternative Facts Have No Place in Science Christine Laine and Darren B. Taichman Metrics Cited byThe Effects of the “War on Science” Frame on Scientists’ CredibilityMarching for the myth of scienceAlternative Facts Have No Place in ScienceChristine Laine, MD, MPH and Darren B. Taichman, MD, PhD 20 June 2017Volume 166, Issue 12Page: 899-900KeywordsBreast cancerConflicts of interestDisclosureEnvironmental healthForecastingGlobal healthHIVPrevention, policy, and public healthScience policyScientists ePublished: 18 April 2017 Issue Published: 20 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Factors Affecting the Cost of Airplanes and Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
Authors: Neil J. Stone
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology 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 Cardiology journal
Tumor Sidedness and Prognosis in Colorectal Cancer
Authors: Yusuf Karakas, Omer Dizdar
Journal: JAMA Oncology (2017)

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