tbuckley/cabot-search huggingface dataset:
Direct Intracerebral Delivery of Cintredekin Besudotox (IL13-PE38QQR) in Recurrent Malignant Glioma: A Report by the Cintredekin Besudotox Intraparenchymal Study Group
Authors: Sandeep Kunwar, Michael D. Prados, Susan M. Chang, Mitchel S. Berger, Frederick F. Lang, Joseph M. Piepmeier, John H. Sampson, Zvi Ram, Philip H. Gutin, Robert D. Gibbons, Kenneth D. Aldape, David J. Croteau, Jeffrey W. Sherman, Raj K. Puri
Journal: Journal of Clinical Oncology (2007)

Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin (PE38QQR). Convection-enhanced delivery (CED) is a locoregional-administration method leading to high-tissue concentrations with large volume of distributions. We assessed the use of intracerebral CED to deliver CB in patients with recurrent malignant glioma (MG).Three phase I clinical studies evaluated intracerebral CED of CB along with tumor resection. The main objectives were to assess the tolerability of various concentrations and infusion durations; tissue distribution; and methods for optimizing delivery. All patients underwent tumor resection followed by a single intraparenchymal infusion (in addition to the intraparenchymal one following resection), with a portion of patients who had a preresection intratumoral infusion.A total of 51 patients with MG were treated including 46 patients with GBM. The maximum tolerated intraparenchymal concentration was 0.5 microg/mL and tumor necrosis was observed at this concentration. Infusion durations of up to 6 days were well tolerated. Postoperative catheter placement appears to be important for optimal drug distribution. CB- and procedure-related adverse events were primarily limited to the CNS. Overall median survival for GBM patients is 42.7 weeks and 55.6 weeks for patients with optimally positioned catheters with patient follow-up extending beyond 5 years.CB appears to have a favorable risk-benefit profile. CED is a complex delivery method requiring catheter placement via a second procedure to achieve accurate catheter positioning, better drug distribution, and better outcome.
Abstract 2389: uPA and uPAR siRNA inhibits angiogenesis by blocking nuclear localization of angiogenin and angiopoietin1 signaling in glioblastoma cell lines
Authors: Hari Raghu, Ju Han Song, Daniel Fassett, Jeffrey D. Klopfenstein, Dzung H. Dinh, Meena Gujrati, Jasti S. Rao
Journal: Cancer Research (2010)

Abstract Transcriptional inactivation of uPA and uPAR system in the glioblastoma cell line SNB19 inhibited angiogenesis both in vitro and in vivo. To decipher this mechanism and extend our studies to other glioblastoma cell lines, U87MG and U87 SPARC-overexpressing cell lines were subjected to uPA, uPAR and U2 (bicistronic construct against uPA and uPAR) downregulation by siRNA. In the present study, the bicistronic construct against uPA and uPAR caused significant inhibition of angiogenesis by in vitro angiogenesis assay and in vivo dorsal skin fold chamber models in both cell lines. Increased apoptosis was seen in siRNA downregulated gliomablastoma cells when compared with control cells by FACS analysis. MTT assay revealed significant inhibition of proliferation by U2 siRNA treatment in both cell lines. Transfection with siRNA against uPA and uPAR in co-cultures of glioma cells with endothelial cells showed significant inhibition of angiopoeitin1, IL-6, GRO and GM-CSF while SPARC-overexpressing U87 cells had decreased secretion of angiogenin, GRO, MCP-1, PDGFBB, VEGF and angiopoietin1 by protein array analysis. Bicistronic construct showed decreased levels of angiogenin by ELISA and Western blot in endothelial cells and in cocultures with cancer cells. Transcriptional inactivation of uPA and uPAR showed significant downregulation of angiogenin-induced phosphorylation of ERK, JNK and Akt signaling in endothelial cells. Nuclear translocation of angiogenin in semi-confluent human umbilical vein endothelial cells treated with conditioned medium from siRNA-transfected U87 SPARC-overexpressing cells was inhibited as shown by Western blot and immunofluorescence analyses. Conditioned medium from U87MG and U87 SPARC-overexpressing cells transfected with uPA, uPAR and U2 siRNA plasmids significantly inhibited the phosphorylation of Tie2 receptor in endothelial cells. uPA and uPAR downregulation significantly downregulated MMP-2 levels by gelatin zymography in co-cultures and in single cultures of cancer cells. Matrix metalloproteinase array analysis showed significant inhibition of MMP-3 in co-cultures of U2-transfected SPARC-overexpressing glioma cells. Overall, our results suggest that the simultaneous downregulation of uPA and uPAR inhibits angiogenesis by inhibition of nuclear localization of angiogenin, angiopoeitin 1 signaling and MMP-2 downregulation in endothelial cells. In summary, these results identify novel mechanisms by which the bicistronic construct against uPA and uPAR inhibits angiogenesis, thereby suggesting the potential use of U2 as an anti-angiogenic agent against glioblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2389.
A newly synthesized photostable retinol derivative (retinyl N-formyl aspartamate) for photodamaged skin: Profilometric evaluation of 24-week study
Authors: Min-Suk Lee, Kyung-Ho Lee, Hong-Sig Sin, Soo-Jong Um, Jin-Wou Kim, Bo-Kyung Koh
Journal: Journal of the American Academy of Dermatology (2006)
French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours
Authors: S Chevillard, Ph Vielh, P Validire, JP Marie, AM Faussat, V Barbu, C Bayle, J Bénard, C Bonnal, J Boutonnat, F Calvo, J Charrier, A Clary, P Colosetti, L Danel-Moore, P Decrémoux, C Delvincourt, F Finat-Duclos, Ph Genne, A Kataki, JC Kouyoumdjian, R Lacave, C Maugard, JL Merlin, M Mousseau, F Pinguet, V Quillien, M Raphael, B Richard, P Verrelle, J Robert
Journal: Leukemia (1997)
Lack of Poly(ADP-Ribose) Polymerase-1 Gene Product Enhances Cellular Sensitivity to Arsenite
Authors: Anuradha Poonepalli, Lakshmidevi Balakrishnan, Aik Kia Khaw, Grace Kah Mun Low, Manikandan Jayapal, Rabindra N. Bhattacharjee, Shizuo Akira, Adayabalam S. Balajee, M. Prakash Hande
Journal: Cancer Research (2005)

Abstract Arsenite (As3+) has long been known to induce cancer and other degenerative diseases. Arsenite exerts its toxicity in part by generating reactive oxygen species. Identification of genetic factors that contribute to arsenic mutagenicity and carcinogenicity is critical for the treatment and prevention of arsenic exposure in human population. As poly(ADP-ribose) polymerase (PARP) is critical for genomic DNA stability, role of PARP-1 was evaluated in arsenic-induced cytotoxic and genotoxic effects. Our study revealed that telomere attrition, probably owing to arsenite-induced oxidative stress, was much more pronounced in PARP-1−/− mouse embryonic fibroblasts (MEF; 40%) compared with PARP-1+/+ MEFs (10-20%). Correlation observed between telomere reduction and apoptotic death in PARP-1 null cells strongly indicates that the telomere attrition might be a trigger for enhanced apoptotic death after arsenite treatment. Elevated DNA damage detected by alkaline comet assay points to an impaired repair ability of arsenite-induced DNA lesions in PARP-1−/− MEFs. Consistent with elevated DNA damage, increased micronuclei induction reflecting gross genomic instability was also observed in arsenite-treated PARP-1−/− MEFs. Microarray analysis has revealed that arsenite treatment altered the expression of about 311 genes majority of which have known functions in cellular responses to stress/external stimulus and cell growth and/or maintenance. Our results suggest an important role for PARP-1 gene product in the maintenance of chromosome-genome stability in response to arsenite-induced DNA damage.
Sixty-Four–Multislice Computed Tomography Image of a Ruptured Coronary Plaque
Authors: Nobuyoshi Tanaka, Mariko Ehara, Jean-François Surmely, Tetsuo Matsubara, Mitsuyasu Terashima, Etsuo Tsuchikane, Osamu Katoh, Takahiko Suzuki
Journal: Circulation (2006)
Patient-Reported Outcomes Supporting Anticancer Product Approvals
Authors: Edwin P. Rock, Dianne L. Kennedy, Melissa H. Furness, William F. Pierce, Richard Pazdur, Laurie B. Burke
Journal: Journal of Clinical Oncology (2007)

In 2006, the US Food and Drug Administration (FDA) published draft guidance to provide recommendations for development, validation, implementation, and interpretation of patient-reported outcome (PRO) measures that can support treatment benefit claims in product labeling. Here, we summarize and discuss FDA approvals of anticancer products in the context of the draft guidance. We identified anticancer product approvals having efficacy claim(s) based at least in part on a PRO. In addition, we collated limitations of PRO instruments commonly submitted for regulatory review over the period from October 1, 2004 to September 30, 2006. From 1995 onward, nine indications were approved for seven anticancer products based at least in part on a PRO. In eight of nine approvals, PRO data supplemented other evidence of clinical benefit. In seven approvals, the PRO measured a single symptom or functional domain that was directly attributable to the treatment benefit observed in the disease. The FDA's draft PRO guidance describes principles that have been used in anticancer product approvals for more than a decade. PRO end points typically support treatment benefit claims that refer to a patient's symptoms or ability to function. Single-item PROs may be acceptable. PRO data should be both internally consistent and aligned with other evidence of clinical benefit. The FDA encourages sponsors to consult with the FDA early in the process of PRO development.
The Expanding Scope of State Legislation
Authors: Fred J. Hellinger
Journal: JAMA (1996)

EACH YEAR dozens of bills that govern the activities of managed care plans are introduced in state legislatures. Often, opponents refer to these as anti-HMO, anti—managed care, or anticoordinated care, and supporters refer to them as patient protection acts or fair managed care acts.  Some of these bills ensure enrollees direct access to certain types of medical specialists without the need for a referral from their primary physician, and others ban exclusive relationships between health plans and physician providers. In addition, more than a dozen bills were introduced in state legislatures in 1995 that set minimum lengths of hospital stays for deliveries.  This study traces the growth of 3 types of state laws that regulate managed care plans (direct-access laws, laws that prohibit exclusivity clauses, and laws that mandate minimum lengths of stay for deliveries). Arguments advocating and resisting these laws are examined along with information about their impact on
Abstract IA13: Finding biomarkers of response to targeted cancer drugs through functional genetics
Authors: Rene Bernards
Journal: Clinical Cancer Research (2012)

Abstract Unresponsiveness to therapy remains a significant problem in the treatment of cancer, also with the new classes of cancer drugs. In my laboratory, we use functional genetic approaches to identify biomarkers that can predict responsiveness to targeted cancer therapeutics; drugs that specifically inhibit molecules or pathways that are often activated in cancer. Nevertheless, it remains poorly explained why a significant number of tumors do not respond to these therapies. We aim to elucidate the molecular pathways that contribute to unresponsiveness to targeted cancer therapeutics using a functional genetic approach. This will yield biomarkers that may be useful to predict how individual patients will respond to these drugs. Furthermore, this work may allow the development of drugs that act in synergy with the established drug to prevent or overcome drug resistance. To identify biomarkers that control tumor cell responsiveness to cancer therapeutics, we use multiple complementary approaches. First, we use genome wide loss-of-function genetic screens (with shRNA interference libraries) in cancer cells that are sensitive to the drug-of-interest to search for genes whose down-regulation confers resistance to the drug-of-interest (resistance screens). In addition, we use shRNA screens with a low dose of the drug to screen for genes whose inhibition enhances the toxicity of the cancer drug (sensitizer screens). As a third approach, we use gain of function genetic screens in which we search for genes whose over-expression modulates drug responsiveness. Once we have identified candidate drug response biomarkers in relevant cell line models, we ask if the expression of these genes is correlated with clinical response to the drug-of-interest. For this, we use tumor samples of cancer patients treated with the drug in question and whose response to therapy is documented. In a fourth and distinct approach we perform high throughput sequencing of the “kinome” (some 600 genes) of tumor samples to identify connections between cancer genotype and drug responses. Examples of these approaches to identify biomarkers of response to different cancer drugs will be presented.
The biophysical basis of hypofiltration in nephrotic humans with membranous nephropathy
Authors: Robert H. Ting, Batya Kristal, Bryan D. Myers
Journal: Kidney International (1994)

Physiologic and morphologic techniques were used to elucidate the determinants of the glomerular filtration rate in 62 nephrotic patients with membranous nephropathy and 104 healthy controls. Renal plasma flow, glomerular filtration rate, afferent oncotic pressure and dextran sieving coefficients were determined. Mathematical models of glomerular filtration were then used to compute likely upper bounds for the ultrafiltration coefficient and pore area/length ratio (a measure of pore density). These upper bounds for each measure of intrinsic ultrafiltration capacity were both depressed by 75% in membranous nephropathy. A corresponding excess of ultrafiltration pressure (versus control), attributable solely to reduced intracapillary oncotic pressure was by 12 mm Hg. Glomerular morphometry revealed peripheral capillary filtration surface area to be enhanced in membranous nephropathy (3.27 x 10(5) vs. 2.03 x 10(5) micron2). However, there was a massive reduction in filtration slit frequency due to epithelial podocyte broadening (336 vs. 1204 slits/mm capillary length) as well as marked thickening of the glomerular basement membrane (1130 vs. 388 nm). We conclude that the latter two findings lower the ultrafiltration coefficient in membranous nephropathy by depressing the hydraulic permeability of the glomerular capillary wall. We propose that this abnormality is solely responsible for the hypofiltration observed in a majority of patients with this disease.
Thousands of women sterilised in Sweden without consent
Authors: C. Armstrong
Journal: BMJ (1997)

The Swedish government is to investigate why thousands of women were forcibly sterilised on eugenic grounds from the 1930s up to the 1970s.

Margot Wallstrom, the minister of health and social affairs, condemned the acts as barbaric and said that a committee would investigate why the practice went on for so long and why it continued even after the horror of similar policies in Nazi Germany was revealed. The committee will also look into why many sterilisations were performed without consent on women who were having abortions.

The Swedish newspaper Dagens Nyheter revealed that up to 60000 people were sterilised on the grounds …
Body Surface Potential Distributions During Idiopathic Ventricular Tachycardia
Authors: Didier Klug, Ange Ferracci, Franck Molin, Marc Dubuc, Pierre Savard, Teresa Kus, François Hélie, René Cardinal, Réginald Nadeau
Journal: Circulation (1995)

Background The purpose of this report is to describe the body surface potential maps (BSPMs) during idiopathic ventricular tachycardia (VT) and to determine what differences exist between different idiopathic VT morphologies. Methods and Results We performed BSPMs during VT on 12 consecutive patients (3 women and 9 men; mean age, 42±13 years) presenting symptomatic idiopathic VT referred to our institution for electrophysiological study. Basal ECG, chest radiograph, and echocardiogram were normal in all patients. Clinical tachycardia showed left bundle branch block pattern (LBBB) in 9 patients, with sustained VT in 5 and nonsustained VT in 4, and right bundle branch block pattern (RBBB) in 3 with sustained VT. We found a unique pattern of BSPMs in each of the 9 patients during idiopathic LBBB VT configuration, whether sustained or nonsustained VT. This pattern appeared at the onset of the QRS and remained stable during the whole QRS complex. The area of minimal potential located in the upper anterior part of the torso was compatible with an origin of VT in the right ventricular outflow tract, as confirmed in 5 patients by successful radiofrequency ablation. We found an evolving pattern with two phases in each of the three RBBB VTs. The electrical axis during the initial part of the QRS could correspond to an endocardial-epicardial vector. The second phase, with a high voltage and area of minimal potential located in the inferior and anterior part of the torso, was compatible with a left ventricular apical origin that was confirmed by epicardial and endocardial mapping during cryosurgery in 1 patient. For all the VTs, the QRS isoarea maps showed the same pattern as the second phase of the QRS. Conclusions Two different BSPM patterns were found. All LBBB VTs had the same stable pattern corresponding to an infundibular origin. All RBBB VTs had an evolving pattern that stabilized in the second part of the QRS complex corresponding to an apical origin.
Abstract 13027: Ex Vivo Induction of Microvascular Network Within the Engineered Three Dimensional Cardiac Tissues Using a Novel Bioreactor System
Authors: Hidekazu Sekine, Tatsuya Shimizu, Izumi Dobashi, Masanori Wada, Masayuki Yamato, Teruo Okano
Journal: Circulation (2011)

Background: In tissue engineering, current methods are limited by the restrictions of passive diffusion, preventing the creation of thick and viable tissues. Therefore, new technologies for making ...
A CASE OF GENERAL GASEOUS EMPHYSEMA WITH GAS CYSTS IN THE BRAIN FORMED AFTER DEATH AND DUE TO BACILLUS MUCOSUS CAPSULATUS, WITH A CONSIDERATION OF THE GAS-PRODUCING PROPERTIES OF CERTAIN MEMBERS OF THIS GROUP IN THE CADAVERS OF ANIMALS
Authors: W. T. Howard
Journal: The Journal of Experimental Medicine (1900)

In the case reported in this article there was septicaemia with special localization of the microorganisms in the brain, with gas cysts of the brain and general gaseous emphysema due to Bacillus mucosus capsulatus (aërogenes group). The bacillus isolated from the organs of this case, as well as other members of the aërogenic group of Bacillus mucosus capsulatus can cause general gaseous emphysema in the cadavers of rabbits, either with or without the intravenous injection of sugar before the animal is killed, the gas, however, being most abundant and rapidly formed in the former case. It is not impossible that some of the published cases of gaseous emphysema in which a bacteriological examination was not made, may have been due to members of the Bacillus mucosus capsulatus group.
Evidence-Based Management of Stroke
Authors: Ian B. Ross
Journal: JAMA (2012)

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Transposition of the Great Arteries
Authors: W. H. PLAUTH, A. S. NADAS, W. F. BERNHARD, R. E. GROSS
Journal: Circulation (1968)

Experience with 74 consecutive patients with transposition of the great arteries treated by palliative methods at the Children's Hospital Medical Center in Boston from June 1950 to September 1966 forms the basis for this report. Four palliative techniques were considered in detail. The specific palliative approach suggested depended on the anatomy and physiology in the individual case. Atrial septal defect creation was used largely for patients with an intact ventricular septum to improve arterial saturation, vent the left atrium, and prevent development of pulmonary vascular obstructive changes. Pulmonary artery banding was the procedure used mainly for infants with large ventricular septal defect, adequate mixing, and pulmonary arterial hypertension. The combined operation was performed on infants with ventricular defect in whom arterial-venous mixing was less than optimal through a relatively small ventricular septal defect. Arterial shunt operations were used for cyanotic infants, not in congestive failure, with ventricular septal defect and severe pulmonic stenosis. The authors recommend palliative surgery in the neonatal period for all patients with transposition of the great arteries, except for the few with type IIA lesions who have just the optimal amount of arterial saturation and absence of congestive heart failure. At present at least an 84% survival rate can be expected from the palliative surgical procedures even in the critically ill infant in the first days of life.
Abstract P5-14-01: Accrual of underrepresented minority women to breast cancer clinical trials in Inland Empire, California.
Authors: Yuan Yuan, Padma Tadi Uppala, John W Morgan, Carlos A Garberoglio, Sharon Lum
Journal: Cancer Research (2012)

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-01.