tbuckley/cabot-search huggingface dataset:
Complete regression of ovarian cancer xenografts following treatment with the recombinant immunocytotoxic protein, VB6-845.
Authors: Jennifer G. Brown, Michele Rasamoelisolo, Jeannick Cizeau, Denis Bosc, Joycelyn Entwistle, Nick Glover, Glen MacDonald
Journal: Cancer Research (2006)

5555   VB6-845 is a recombinant fusion construct consisting of a tumor-targeting Fab linked to de-immunized Bouganin, a type 1 ribosome-inactivating protein (RIP). VB6-845 specifically targets the epithelial cell adhesion molecule (Ep-CAM) that is highly expressed on many different epithelial carcinomas, including ovarian cancer. Ovarian cancer is the fourth most common cause of cancer mortality in women. Advances in surgery and treatment modalities have improved survival, but prognosis remains poor with a five-year survival rate of about 30% indicating the need for more effective treatment. Immunohistochemistry (IHC) determined a high level of VB6-845 immunoreactivity in ovarian primary (>90%) and metastatic (90%) carcinomas. VB6-845 exhibited potent activity against the ovarian Ep-CAM positive cancer cell line, OVCAR-3 as determined using an MTS assay, with an IC 50  of 0.6 nM, (0.26 μg/mL).  In vivo  efficacy of VB6-845 was demonstrated in the OVCAR-3 subcutaneous implanted xenograft model in SCID mice. I.V. administration of 10 & 20 mg/kg of VB6-845 resulted in 100% survival as compared to 27% survival in the untreated group on Day 75. The majority of the mice (80%) dosed at 20 mg/kg were tumor free (p  In vivo  efficacy of VB6-845 also was demonstrated in the OVCAR-3 intraperitoneal (I.P.) implanted xenograft model in Balb/c  Nude  mice. I.P. administration of 10 mg/kg of VB6-845 resulted in 93% survival as compared to 0% in the untreated group on Day 84 (p
Abstract 3742: Detection of EGFR, HER2, HER3 and HER4 homodimerization and heterodimerization using EFC-based cellular assays
Authors: Jane Lamerdin, Abhishek Saharia, Jennifer Lin-Jones, Mimi Nguyen, Hyna Fabionar, Sangeetha Gunturi, Abha Srivastava, Tom Wehrman
Journal: Cancer Research (2014)

Abstract Ligand-induced receptor dimerization is the first functional step in receptor signaling, representing the most proximal, functional read-out for receptor activation. Here we present a novel application of the Enzyme Fragment Complementation system to monitor receptor-receptor interactions at the surface of intact cells, applicable to diverse receptor types such as RTKs, Interleukin receptors, BMP receptors and cytokine receptors, amongst others. For the purpose of this poster, we will focus on the HER family of receptors. It is well understood that the HER family proteins can dimerize with the other members of its family leading to a complicated oncogenic signaling cascade. Surprisingly, existing cellular assays have been unable to faithfully monitor these interactions proximally in a drug discovery setting. We present EFC-based cellular assays that monitor EGFR homodimerization, EGFR-ErbB2 and ErbB2-ErbB3 heterodimerization events at the receptor. The high signal to noise ratio, serum tolerance and reproducibility make these assays ideal for a diverse range of applications for the identification and development of therapeutic small molecules and biologics, including screening, functional characterization, QC lot release assays and neutralizing antibody studies. Citation Format: Jane Lamerdin, Abhishek Saharia, Jennifer Lin-Jones, Mimi Nguyen, Hyna Fabionar, Sangeetha Gunturi, Abha Srivastava, Tom Wehrman. Detection of EGFR, HER2, HER3 and HER4 homodimerization and heterodimerization using EFC-based cellular assays. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3742. doi:10.1158/1538-7445.AM2014-3742
Maintaining Physician Competence and Professionalism
Authors: C. David Naylor, Rocco Gerace, Donald A. Redelmeier
Journal: JAMA (2015)

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
Recurrent Ischemia After Thrombolysis: Importance of Associated Clinical Findings fn1fn1This study was supported by grants from Bayer, New York, New York; CIBA-Corning, Medfield, Massachusetts; Genentech, South San Francisco, California; ICI Pharmaceuticals, Wilmington, Delaware; and Sanofi Pharmaceuticals, Paris, France.
Authors: Amadeo Betriu, Robert M. Califf, Xavier Bosch, Alan Guerci, Amanda L. Stebbins, N.Alejandro Barbagelata, Philip E. Aylward, Alec Vahanian, Frans Van de Werf, Eric J. Topol
Journal: Journal of the American College of Cardiology (1998)
220. Prolonged Biologically Active Transgene Expression Driven by HSV Latency Active Promoter 2 (LAP2) in Brain In Vivo
Authors: Veljko Puskovic, Darren Wolfe, James R. Goss, Shaohua Hang, Joseph C. Glorioso, Marina Mata, David J. Finnk
Journal: Molecular Therapy (2004)

The herpes simplex virus (HSV) latency associated promoter (LAP2) is a transposable element that drives life-long expression of latency associated transcripts (LATs) from latent HSV genomes. We examined the ability of this promoter to drive prolonged expression of a biologically active transgene from latent HSV vector genomes in brain in vivo using the 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson disease. Animals injected with an HSV vector with GDNF under the control of LAP2 five and a half months before 6-OHDA injection showed preservation dopaminergic neuron function in the face of 6-OHDA toxicity measured by amphetamine-induced rotation, number of tyrosine hydroxylase (TH) neurons in the substantia nigra (SN), and immunoreactivity for TH and the dopamine transporter (DAT) in striatum determined 6 months after vector inoculation. The amount of GDNF produced in injected SN determined by ELISA remained stable at 1–2 pg/mg over 6 months. Mice inoculated with the LAP2-GDNF HSV vector followed by 3 months of daily low dose MPTP injection were substantially protected against the consequences of that treatment measured by weekly behavioral testing (contralateral pellet retrieval in a staircase apparatus) and by histologic measures including number of TH-IR neurons in SN, and TH-IR and DAT-IR in striatum determined at the conclusion of the experiment 13 weeks after vector inoculation. These studies demonstrate that the HSV LAP2 promoter element provides prolonged expression of relevant amounts of a transgene to produce significant biological effects in brain in vivo over the course of many months.
Science, medicine, and the future: Molecular genetic approaches to understanding disease
Authors: J. Savill
Journal: BMJ (1997)

<h3>Abstract</h3> Molecular genetics has greatly increased the understanding of diseases in which there is a single gene defect such as cystic fibrosis. Discovering the gene responsible and its function not only helps determine the pathogenesis of the disease but also offers a possible treatment-gene therapy. Polygenic disorders such as diabetes may soon yield their secrets to the same approach. Animal models of genetic diseases are proving useful research tools, and transgenesis has made xenografting possible. Furthermore, antisense technology allows specific inhibition of undesirably overexpressed genes such as those driving unwanted vascular cell proliferation and restenosis after angioplasty. The completion of the human genome project should make the search for “disease” genes much quicker and will increase still further the importance of these gene based approaches toward diseases.
Germany turns away UK trained GP
Authors: Tessa Richards
Journal: BMJ (2001)

The European Commission is considering mounting legal action against Germany for non-recognition of UK training of GPs. The case that has brought the commission to this point is that of Dr Helko Schenk, who is currently working as a GP in south west England.

Dr Schenk did his undergraduate training in Germany but has worked in the United Kingdom since 1995. After two years of junior and senior house officer jobs he completed a three year general practice vocational training course, which finished last August. Despite being …
Abstract 252: Feasibility of Three Dimensional Anatomic, Dynamic and Perfusion Imaging of Myocardial Scar Using Contrast Enhanced Multi-Detector Computer Tomography to Guide Ventricular Tachycardia Ablations
Authors: Jing Tian, Jean Jeudy, Mark Smith, Peng Lei, Aharon Turgeman, Aharon Abbo, Robert Peters, Magdi Saba, Stephen Shorofsky, Timm Dickfeld
Journal: Circulation (2009)
Indications for liver transplant and AASLD guidelines
Authors: Manish Thapar, Herbert L. Bonkovsky
Journal: Hepatology (2014)

Potential conflict of interest: Dr. Bonkovsky consults, advises, and received grants from Clinuvel. He consults and advises Recordati and Alnylam. He received grants from Vertex. To the Editor: We read with great interest the recently updated AASLD Practice Guidelines published in the March issue of Hepatology titled “Evaluation for Liver Transplantation in Adults.”1 We commend Dr. Martin and colleagues for undertaking an extensive review of the literature. We think it important for your readers to be aware that, among the indications for liver transplant, other rare disorders should be included. Specifically, we write about growing interest in and a growing body of literature indicating that liver transplantation is curative for severe, unremitting acute intermittent porphyria (AIP).2 This was first described in 2004 and, thus far, most cases have been done in Europe.4 Recently, the first liver transplantation for AIP in the United States was performed with excellent success and prompt cure at Mt. Sinai Medical Center, NYC (Liu et al., pers. commun.). It is also worth reminding readers that erythropoietic protoporphyria (EPP) with pigmentary cirrhosis is a well‐established indication for liver or combined liver/bone marrow transplantation. Numerous case reports and publications in various peer‐reviewed journals attest to the role of liver or combined liver/bone marrow transplantation in patients with chronic liver disease secondary to EPP.5 In fact, among the porphyrias, chronic liver disease in EPP is probably the best established indication for liver transplant. We recently published a review article assessing the role of liver transplantation in porphyria.7 Because of the growing influence of AASLD guidelines for clinical practice and decisions regarding reimbursement, etc., we hope that the AASLD guidelines will soon be amended to take into account liver transplantation for carefully selected patients with porphyrias.
The problems of monitoring response to chemotherapy in subcutaneously implanted 9L glioma using apparent diffusion coefficient of water and 23Na magnetic resonance imaging
Authors: Andriy Babsky, Hong Zhang, S. K. Hekmatyar, Navin Bansal
Journal: Clinical Cancer Research (2006)

B76   Measurements of parameters such as apparent diffusion coefficient (ADC) of water and tissue Na +  by magnetic resonance (MR) techniques have been suggested as noninvasive methods for predicting and/or monitoring response to therapy (1, 2). We and others have found that effective chemotherapy of subcutaneously (sc) implanted Radiation Induced Fibrosarcome (RIF-1) in mice with cyclophosphamide (1) and 5-fluorouracil (3), as well as, chemotherapy of intracranial 9L glioma in rats with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (1) correlate with increases in both total tumor tissue  23 Na signal intensity (SI) and water ADC in the first 3-5 post-treatment days. The most frequently cited hypothesis explaining an increase in tumor water ADC and  23 Na SI following therapy is that tumor cell death by apoptosis or necrosis invoke a net increase in extracellular space (ECS), an environment of assumed fast-diffusing water and high [Na + ] (1, 4). However, this clarification does not explain our results of BCNU treatment of sc-implanted 9L glioma. We have found that in sc-implanted 9L glioma  23 Na SI and water ADC significantly increase with growth in untreated control and non-responsive glioma, while in BCNU-responsive glioma both  23 Na SI and water ADC were almost unchanged (5). It appears the increase in water ADC and  23 Na SI after chemotherapy is not general phenomena resulting from an increase in ECS. Furthermore, in sc-implanted 9L glioma, Winter et al. (6) did not find any changes in the relative ECS, explaining the lower [Na + ] t  in BCNU-treated tumors by improvement of tumor oxygenation and perfusion. We hypothesized that the different results in sc-implanted and intracranial glioma could be caused by location of tumors. However, Schepkin et al. recently reported the increase in water ADC and  23 Na SI in sc-implanted 9L glioma treated by BNCU (7). We assumed that the source of cell culture can play a role in different effects of BCNU. In our study, we used 9L cells from American Type Culture Collection (ATCC), while others (1, 7) used 9L cells from Brain Tumor Research Center, UCSF. Our preliminary results show a one week delay in the sc-growth of 9L glioma from ATCC compared to the tumor growth initiated by cells from UCSF. Additional estimation should be done to evaluate the possible role of type of anesthesia and tumor size in efficiency of BCNU treatment in experimental 9L glioma.References: (1) Schepkin et al. MRM, 53: 85-92, 2005; (2) Babsky et al. Neoplasia, 7: 658-66, 2005; (3) Babsky et al. ISMRM, p.1767, 2006; (4) Ross et al. Eur J Cancer, 38: 2147-56, 2002; (5) Babsky et al. JMRI, 24: 132-9, 2006; (6) Winter et al. Cancer Res 61: 2002-7, 2001; (7) Schepkin et al. MRI, 24: 273-8, 2006.
Abstract #5561: CKD-516, a novel tubulin-binding agent shows marked antitumor activity against murine and human solid tumors
Authors: Kyung Joo Lee, Soo Jin Kim, Gyu Tae Park, Byeong Hoon Han, Jae Hoon Choi, In-Chang Hwang, Jaekwang Lee, Hojin Choi, Young Hoon Kim, Dal-Hyun Kim, Sungsook Lee, Chung Il Hong
Journal: Cancer Research (2009)

In recent years, tubulin-binding agents such as CA4P and AC7700 have received much attention as a novel approach which can overcome many limitations of the conventional cytotoxic agents. In addition to their ability to inhibit microtubule assembly by binding to tubulin monomers resulting in cell-cycle arrest, tubulin binders also target tumor endothelial cells, which results in a rapid occlusion of tumor vasculature, leading to vascular shutdown. The aim of this study was to evaluate the efficacy of CKD-516, a prodrug of novel tubulin-binding agent S-516, in preclinical murine and human tumor models. In  in vitro  study, S-516 was found to be superior to AC7739 (parent molecule of its prodrug, AC7700) in terms of cytotoxicity against HL60 (IC 50  = 5 nM vs. 15 nM), tubulin polymerization inhibition (IC 50  = 4.3 \#956;M vs. 6.5 \#956;M), and HUVEC (human vascular endothelial cells) tube disruption assay. Moreover, treatment of HL60 with S-516 led to G 2 -M arrest and induced apoptosis at lower concentration than AC7739. CKD-516, a prodrug of S-516, is water-soluble (>100 mg/ml) and showed a significant  in vivo  antitumor activity in murine tumor models (CT26 and LLC): in CT26, IR = 33% at 5 mg/kg, 54% at 10 mg/kg, and 83% at 20 mg/kg, respectively (Q4D x 4, ip, p 3 , CKD-516 also demonstrated an excellent efficacy (IR = 70% at 10 mg/kg vs. 63% at 100 mg/kg of AC7700). CKD-516 was also highly efficacious (IR = 69% at 10 mg/kg) in a drug resistant cell line (HCT15) in which paclitaxel was devoid of activity. In a lung metastasis model where murine melanoma (B16BL6) was grafted to tail vein of mouse, CKD-516 at 5 and 10 mg/kg, ip, significantly suppressed the metastasis of tumor to lung (p   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5561.
Abstract P352: Is Brain Natriuretic Peptide or Pro- Brain Natriuretic Peptide of value for Early Cardiovascular Disease Risk Stratification in asymptomatic Subjects?
Authors: Mahfouz El Shahawy, Omar Y El Shahawy, Miglena O Entcheva
Journal: Circulation (2014)

Introduction: There has been much discussion in recent years about the use of Brain natriuretic peptide (BNP) or Pro-brain natriuretic peptide (Pro-BNP) for cardiovascular disease (CVD) risk stratification. The purpose of this study is to assess the association between the presence of abnormal BNP/pro BNP with Left ventricular Hypertrophy (LVH) in asymptomatic subjects with or without hypertension and their value for early CVD risk stratification. Methods: We evaluated 2230 subjects aged 23-80 years, who underwent screening for CVD risk using Early CVD Risk Score (ECVDRS), also known as Rasmussen Risk Score (RRS). ECVDRS consists of 10 non-invasive tests: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post mild exercise (BP PME), Carotid Intima Media Thickness (CIMT), abdominal aorta ultrasound, retinal photography, microalbuminuria, electrocardiogram (ECG), left ventricular ultrasound, and BNP/Pro-BNP. Results: Among the 2230 asymptomatic participants, we analyzed 933 who were treated by at least one or more cardiovascular medication for Diabetes, Hypertension (HTN) or Hyperlipidemia. Our hypothesis was that asymptomatic subjects with LVH have a significantly higher BNP/ProBNP values than those without LVH independent of HTN management. We used 3 Chi-square tests to test the independence between the two groups (with or without LVH) regarding their BNP/ProBNP status for the whole sample and further stratified by their HTN control. The findings in three tests were highly significant; the proportion of abnormal LVH was 0.17 and 0.39 respectively with normal vs elevated BNP/ProBNP for the whole sample, χ 2 (1, N = 933) = 36.693, p &lt; 0.001. When we stratified by HTN control, with uncontrolled HTN the proportion of abnormal LVH was 0.25 and 0.46 respectively with the normal vs elevated BNP/ProBNP, χ 2 (1, N = 271) = 11.983, p =0.0005. Among participants with controlled HTN the proportion of abnormal LVH was 0.15 and 0.33 respectively with normal vs elevated BNP/ProBNP, χ 2 (1, N = 662) = 18.257, p &lt; 0.001. Conclusions: Abnormal BNP/pro-BNP levels are significantly associated with abnormal LVH findings in asymptomatic subjects independent of their HTN control. Thus, ProBNP/BNP could be considered an important follow up test for early detection of serious CV structural abnormality like LVH during the management of patients with HTN regardless of the degree of their HTN control. This finding may justify a more aggressive treatment approach and close monitoring with BNP/ProBNP as a possible screener for CVD manifestations like LVH in HTN patients.
Abstract 156: Autophagic degradation of granzyme B impairs NK-mediated killing of hypoxic tumor cells
Authors: Joanna Baginska, Elodie Viry, Guy Berchem, Aurélie Poli, Muhammad Zaeem Noman, Kris van Moer, Sandrine Medves, Takouhie Mgrditchian, Jacques Zimmer, Anais Oudin, Simone P. Niclou, R. Chris Bleackley, Salem Chouaib, Bassam Janji
Journal: Cancer Research (2014)

Abstract Natural killer (NK) cells are effectors of the innate immune system, able to kill cancer cells through the release of the cytotoxic protease granzyme B. NK-based therapies have recently emerged as promising anticancer strategies. However, it is well established that hypoxic tumor microenvironment interferes with the antitumor function of immune cells and constitutes a major obstacle for defining cancer immunotherapies. Recent studies demonstrated that autophagy regulates the innate immune response by mechanisms which are not fully understood. In this study, we showed that hypoxia decreases breast cancer cell susceptibility to NK-mediated lysis by a mechanism involving the activation of autophagy in tumor cells. Targeting autophagy was sufficient to restore NK-mediated tumor cell killing. We showed that the resistance of hypoxic tumor cells was neither related to a defect in their recognition by NK cells, nor to a defect in the cytolytic function of NK cells toward hypoxic cells. We provided evidence that autophagy activation degrades NK-derived granzyme B in lysosomes of hypoxic cells making them less sensitive to NK-mediated killing. Genetic and pharmacological inhibition of autophagy restored granzyme B levels and reverted the resistance of hypoxic cells in vitro. Our results highlight autophagy as a critical factor in modulating NK-mediated anti-tumor immune response. We have validated this concept in vivo by showing that targeting autophagy significantly improved NK-mediated tumor shrinking in breast and melanoma models. This study provides a cutting-edge advance in our understanding of how hypoxia-induced autophagy impairs NK-mediated lysis and paves the way for formulating more effective NK-based antitumor therapy by combining autophagy inhibitors. Citation Format: Joanna Baginska, Elodie Viry, Guy Berchem, Aurélie Poli, Muhammad Zaeem Noman, Kris van Moer, Sandrine Medves, Takouhie Mgrditchian, Jacques Zimmer, Anais Oudin, Simone P. Niclou, R. Chris Bleackley, Salem Chouaib, Bassam Janji. Autophagic degradation of granzyme B impairs NK-mediated killing of hypoxic tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 156. doi:10.1158/1538-7445.AM2014-156
Stress Without Distress.
Authors: Hans Selye
Journal: Annals of Internal Medicine (1974)

Stress is “the nonspecific response of the body to any demand made upon it,” that is, the rate at which we live at any one moment. All living beings are constantly under stress and anything, pleasant or unpleasant, that speeds up the intensity of life, causes a temporary increase in stress, the wear and tear exerted upon the body. A painful blow and a passionate kiss can be equally stressful.