tbuckley/cabot-search huggingface dataset:
Activity and safety of sunitinib in combination with trastuzumab for the treatment of metastatic breast cancer: initial results from a phase II study.
Authors: T Bachelot, A Lluch, M Gutierrez, MM Martin, MF Kozloff, C Prady, V Tassell, K Kern, X Huang, S Verma, J Blay
Journal: Cancer Research (2009)

Abstract Abstract #4115 Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, FLT3, and CSF-1R, with proven single-agent activity in pts with advanced BC. Trastuzumab (T) is indicated as both monotherapy for second-line treatment and in combination with taxane-based therapies for first-line treatment of metastatic BC. This study investigates the activity and safety/tolerability of SU administered in combination with T in pts with advanced, HER2+ BC.&amp;#x2028; Materials and methods: Eligible pts have unresectable, locally recurrent or metastatic HER2+ BC. Pts received SU at a starting dose of 37.5 mg/d po continuous daily dosing (CDD). T was administered iv wkly (loading 4 mg/kg then wkly 2 mg/kg) or q3w (loading 8 mg/kg then 6 mg/kg q3w). Due to changes in standard of care, the trial was amended from a randomized, placebo controlled design, to a single-arm study, and eligibility criteria were changed to allow inclusion of pts who had previously received CT in the first-line setting. Previous treatment with T (± lapatinib) was also permitted. The planned sample size is 53 pts and the primary endpoint is ORR.&amp;#x2028; Results: In this ongoing trial, a total of 49 pts have been enrolled to date (6 pts under the original protocol and 43 under the amendment). All 43 pts enrolled under the amendment were evaluable for safety/tolerability, and antitumor activity, measured by RECIST. As of May 2008, 25 pts continue on study and 18 have discontinued, 4 due to AEs. Pts started a total of 167 cycles of treatment with a median of 4 cycles/pt (range: 1–8). The planned dose of SU (37.5 mg/d) was maintained in 31/43 pts (72%). It was reduced to 25 mg/d in 12/43 pts (28%). One pt achieved a CR and 10 a PR. SD occurred in 20 pts and PD in 6 pts. This translated into an ORR of 26% (95% CI, 13.5–41.2) and a clinical benefit rate of 35% (95% CI, 21.0–50.9). Median PFS was 25.3 wks (95% CI, 19.3–32.0). The most common treatment-related AEs were diarrhea (55.8%), asthenia (48.8%) and hypertension (37.2%) of which most were G1 or 2. The most frequent G3 AEs were neutropenia (14%) and asthenia (11.6%). There were 2 treatment-related G4 events: thrombocytopenia (2.3%) and LVEF decline (2.3%). There was 1 treatment-related G5 AE (cardiogenic shock).&amp;#x2028; Conclusions: SU 37.5 mg/d on a CDD schedule in combination with T (wkly or q3w) appears to have a manageable safety profile and antitumor activity in pts previously treated for advanced HER2+ BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4115.
Acute cholecystitis from metastatic melanoma to the gall-bladder in a patient with a low-risk melanoma
Authors: R.G.B. LANGLEY, E.M. BAILEY, A.J. SOBER
Journal: British Journal of Dermatology (1997)

Metastatic melanoma to the gall-bladder producing symptoms which mimic cholecystitis is an uncommon and unusual clinical presentation of metastatic disease. We present a case of a 40-year-old women who initially had a thin primary cutaneous melanoma, and later presented with acute abdominal pain which was diagnosed as acute cholecystitis. Pathological review of the gall-bladder revealed metastatic melanoma.
The liver and IgA: Immunological, cell biological and clinical implications
Authors: William R. Brown, Thomas M. Kloppel
Journal: Hepatology (1989)

Secretory immunoglobulin A is the characteristic and predominant immunoglobulin of the mucosal immune system; it participates in immunological protection at the level of mucous membrane surfaces. During the past 10 to 15 years, a great deal of experimental and clinical evidence has shown that the liver is very much involved in the sIgA system. In certain animals (rats, mice, rabbits), polymeric forms of IgA are efficiently cleared by the liver and transported into bile by a receptor-mediated vesicular pathway across hepatocytes. Taking advantage of this easily accessible pathway, investigators have defined many of the events in the external secretion of pIgA, including details about the synthesis and secretion of its receptor, secretory component. In the rat hepatocyte, secretory component is synthesized as a transmembrane glycoprotein and is expressed preferentially on the sinusoidal plasma membrane; circulating pIgA that binds to secretory component is internalized into endocytic vesicles and transported across the hepatocyte to the bile canalicular membrane, where the pIgA is released into bile as a soluble complex with a portion of the secretory component, the complex being secretory IgA. In some other animals (dog, guinea pig, sheep) as well as man, biliary epithelial cells, not hepatocytes, express secretory component and perform the transcytosis and secretion of pIgA into bile. In those species, much of the pIgA that reaches bile is synthesized locally in plasma cells that populate the biliary tree; this design is analogous to the release of sIgA into various mucosae in the body. The major biological functions ascribed to the secretion of IgA into bile are enhancement of immunological defense of the biliary and upper intestinal tracts and the clearance of harmful antigens from the circulation as IgA-antigen complexes. However, the importance of biliary IgA antibodies is largely unclarified, and man lacks the capacity for effective clearance of IgA-antigen complexes via the secretory component-mediated transhepatocellular pathway; whether this deficit contributes to the propensity for man to develop IgA immune complex diseases should be clarified. Among liver diseases, alcoholic disease is most closely linked to alterations in IgA metabolism. This association is manifested principally by the deposition of IgA along the sinusoids in the livers of the majority of alcoholics and in the renal mesangium of many. The IgA1 subclass of IgA predominates in the IgA deposits in both tissues; the possibility that this predominance is related to abnormalities in the removal of circulating IgA1 by asialoglycoprotein receptors on hepatocytes is an intriguing consideration. Thus, the liver plays a unique role in mucosal immunity and in the physiology of IgA in normal and disease states. Further study of the associations between the liver and IgA, particularly in man, is clearly needed.
Response of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine. Evidence for myocardial receptor-mediated effects.
Authors: B B Lerman
Journal: Circulation (1993)

Reentrant ventricular tachycardia (VT) is known to be insensitive to the nucleoside adenosine. However, we have previously identified a form of nonreentrant, catecholamine-mediated VT that can be initiated with rapid pacing, demonstrates cycle length dependence, and is sensitive to exogenous adenosine as well as to the Valsalva maneuver. The mechanism of this tachycardia is thought to be due to a catecholamine-induced, cAMP-mediated increase in intracellular calcium, resulting in delayed afterdepolarizations and triggered activity. The antiarrhythmic effects of exogenous adenosine and Valsalva on this form of VT may be due to receptor-mediated inhibition of adenylate cyclase or to noncardiac receptor-mediated effects, i.e., exogenous adenosine may modulate VT through alterations in autonomic tone by activation of arterial chemoreceptors, and Valsalva has been shown to decrease venous return, resulting in a reduction in cardiac dimensions and myocardial stretch. To clarify this issue and circumvent both autonomic and noncardiac receptor effects, the response of nonreentrant catecholamine-mediated VT to endogenous adenosine and acetylcholine was evaluated.Group 1 (n = 8): Dipyridamole (0.56 mg/kg i.v.), a nucleoside transport blocker that potentiates the effects of endogenous adenosine, reproducibly abolished sustained nonreentrant, nonautomatic, catecholamine-mediated VT in the five patients in whom it was evaluated. VT recurred with the addition of aminophylline, a competitive adenosine A1-receptor antagonist. Edrophonium (10 mg i.v.), a cholinesterase inhibitor that potentiates the effects of acetylcholine at the muscarinic cholinergic receptor, terminated VT in four of four patients, an effect that was reversed by atropine. Group 2 (n = 6): In patients with reentrant VT, dipyridamole and edrophonium had no effect on VT cycle length or duration. Group 3 (n = 4): Adenosine and vagal maneuvers had no effect on catecholamine-mediated VT caused by automaticity in three of four patients tested. In one patient, adenosine transiently suppressed VT (< 5 seconds), after which it spontaneously resumed.The results of this study further delineate the mechanism of a newly recognized form of clinical VT. It can be identified by termination of the tachycardia in response to activation of the adenosine A1 or muscarinic cholinergic receptor, which results in inhibition of adenylate cyclase. These receptor-mediated effects appear to be specific for identifying nonreentrant, nonautomatic, catecholamine-mediated VT.
Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.
Authors: A Fox-Robichaud, D Payne, S U Hasan, L Ostrovsky, T Fairhead, P Reinhardt, P Kubes
Journal: Journal of Clinical Investigation (1998)

Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NO-depleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations.
The Clinical Acceleration of Healing With a Cartilage Preparation
Authors: John F. Prudden
Journal: JAMA (1965)

A controlled study of the wound acceleration induced by fine-grind acid-pepsin digested calf tracheal cartilage has been made in 15 human volunteers. Small paired skin incisions were made in precisely corresponding anatomical sites, and one wound treated with the powder by atomization while the other wound served as the control. Closure was identical. After varying (7 to 14 days) intervals of time, the wounds were excised with a margin and the resulting defects closed. The tensile strengths of the wounds were then determined. In 12 of the 15 wound pairs, the treated wound was stronger. The overall percentage increase in tensile strength resulting from the treatment was 42%, and the difference is statistically highly significant. The effectiveness of this material in the acceleration of human wound healing is considered established.
Early detection of lung involvement in lysinuric protein intolerance: role of high-resolution computed tomography and radioisotopic methods.
Authors: F Santamaria, G Parenti, G Guidi, A Rotondo, G Grillo, M R Larocca, L Celentano, P Strisciuglio, G Sebastio, G Andria
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Pulmonary disease of unknown etiology is a potentially fatal complication in patients with lysinuric protein intolerance (LPI), an autosomal recessive disorder caused by the defective transport of cationic amino acids. Lung involvement was investigated in nine Italian LPI patients through pulmonary function tests and lung imaging studies consisting of conventional chest radiography, high-resolution computed tomography (HRCT), and perfusion and ventilation scintigraphy. One 10-yr-old patient died of severe respiratory insufficiency from alveolar proteinosis. All of the remaining patients were asymptomatic at the time of the study, although HRCT scans revealed signs of lung involvement defined by the presence of acinar nodules, inter- and/or intralobular thickening of the interstitial septa, and subpleural cysts in five of the patients. Radioisotope studies showed an uneven distribution of perfusion and ventilation, and confirmed the presence of segmental and/or diffuse pulmonary functional defects. No abnormalities of pulmonary function were evident, and answers to a questionnaire excluded primary coexisting lung disease. In patients with LPI, including those without clinical and functional impairment, HRCT and radioisotopic studies appear to be the most sensitive methods for the early diagnosis of lung disease and correct assessment of its progression.
Catheter Pacing in Complete Heart Block
Authors: Alvin J. Gordon
Journal: JAMA (1965)

The bipolar catheter pacemaker was used as a temporary measure in 58 patients with complete heart block. The external jugular veins were the preferred sites of passage, and a fluoroscopic image intensifier was almost a necessity. Complications were frequent including two deaths during catheterization and two later deaths. Failure to pace was usually caused by malposition or breakage of the catheter, poor electrical connections, or run-down batteries. Investigation of such failure should include a survey of the pacemaker artifact in the standard electrocardiogram and the recording of endocardial leads from the catheter, in addition to x-ray studies.
Thirteen-year follow-up of early intervention with an inhaled corticosteroid in patients with asthma
Authors: Tari Haahtela, Klaus Tamminen, Tuomo Kava, L. Pekka Malmberg, Paula Rytilä, Kurt Nikander, Tore Persson, Olof Selroos
Journal: Journal of Allergy and Clinical Immunology (2009)
ITAM-Based Interaction of ERM Proteins with Syk Mediates Signaling by the Leukocyte Adhesion Receptor PSGL-1
Authors: Ana Urzainqui, Juan M Serrador, Fernando Viedma, Marı́a Yáñez-Mó, Antonio Rodrı́guez, Angel L Corbı́, Jose L Alonso-Lebrero, Alfonso Luque, Marcel Deckert, Jesús Vázquez, Francisco Sánchez-Madrid
Journal: Immunity (2002)
Disruption of the Cr2 Locus Results in a Reduction in B-1a Cells and in an Impaired B Cell Response to T-Dependent Antigen
Authors: Joseph M Ahearn, Michael B Fischer, Denise Croix, Siegfried Goerg, Minghe Ma, Junrong Xia, Xioning Zhou, Robert G Howard, Thomas L Rothstein, Michael C Carroll
Journal: Immunity (1996)

Covalent attachment of activated products of the third component of complement to antigen enhances its immunogenicity, but the mechanism is not clear. This effect is mediated by specific receptors, mCR1 (CD35) and mCR2 (CD21), expressed primarily on B cells and follicular dendritic cells in mice. To dissect the role of mCR1 and mCR2 in the humoral response, we have disrupted the Cr2 locus to generate mice deficient in both receptors. The deficient mice (Cr2−/−) were found to have a reduction in the CD5+ population of peritoneal B-1 cells, although their serum IgM levels were within the range of normal mice. Moreover, Cr2−/− mice had a severe defect in their humoral response to T-dependent antigens that was characterized by a reduction in serum antibody titers and in the number and size of germinal centers within splenic follicles. Reconstitution of the deficient mice with bone marrow from MHC-matched Cr2+/+ donors corrected the defect, demonstrating that the defect was due to B cells themselves. These results indicate an obligatory role of B cell complement receptors in responses of the B cells to protein antigens.
Evidence from mucin core protein expression that some Paget's disease on areola can be of extramammary-like histogenesis and part of multisite disease
Authors: T. Ohnishi, S. Shibuya, I. Nemoto, S. Koike, H. Takizawa, T. Suzuki, S. Watanabe
Journal: British Journal of Dermatology (2004)

Journal Article Evidence from mucin core protein expression that some Paget's disease on areola can be of extramammary‐like histogenesis and part of multisite disease Get access T. Ohnishi, T. Ohnishi Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Takamitsu Ohnishi. E‐mail: ohnishi@med.teikyo‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Shibuya, S. Shibuya Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar I. Nemoto, I. Nemoto Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Koike, S. Koike Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Takizawa, H. Takizawa Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Suzuki, T. Suzuki Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Watanabe S. Watanabe Department of Dermatology, Teikyo University School of Medicine, 11‐1 Kaga‐2, Itabashi‐ku, Tokyo 173‐8605, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 3, 1 September 2004, Pages 688–692, https://doi.org/10.1111/j.1365-2133.2004.06087.x Published: 01 September 2004 Article history Accepted: 18 February 2004 Published: 01 September 2004
'Foil Tab' Aspiration and Retropharyngeal Abscess in a Toddler
Authors: Mitchell N. Ross
Journal: JAMA (1988)

To the Editor. —  Foreign body ingestion and aspiration constitute sources of morbidity and mortality in children younger than 4 years old. 1 These objects are usually foodstuffs or small objects that are within the child's reach. In previous years, the throwaway aluminum   from beverage cans were aspirated by toddlers 2 ; now they have been almost completely replaced by pop tops that remain attached to the container. Some beverages, however, are now packaged in containers with disposable  tabs, and these too can be aspirated.  Recently, we cared for a child who aspirated a foil tab and presented with a retropharyngeal abscess.  Report of a Case.—  A 13-month-old girl was referred to us with a three-day history of fevers, an inability to take anything by mouth, and constant drooling. One day prior to referral she was evaluated for these problems with an anterior-posterior neck roentgenogram that demonstrated no
Binding of Cardnoembryonic Antigen (CEA) to Concanavalin A-Sepharose: Storage of High-Specific-Activity 125I-CEA2
Authors: Gary S. David, Ralph A. Reisfeld
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Binding of Cardnoembryonic Antigen (CEA) to Concanavalin A-Sepharose: Storage of High-Specific-Activity 125I-CEA Get access Gary S. David, Gary S. David Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph A. Reisfeld Ralph A. Reisfeld 3Department of Experimental Pathology, Scripps Clinic and Research Foundation, 476 Prospect St., La Jolla, Callif. 92037. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 4, October 1974, Pages 1005–1010, https://doi.org/10.1093/jnci/53.4.1005 Published: 01 October 1974 Article history Received: 06 February 1974 Accepted: 21 June 1974 Published: 01 October 1974
Hyperpolarized 13C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and Grading
Authors: Mark J. Albers, Robert Bok, Albert P. Chen, Charles H. Cunningham, Matt L. Zierhut, Vickie Yi Zhang, Susan J. Kohler, James Tropp, Ralph E. Hurd, Yi-Fen Yen, Sarah J. Nelson, Daniel B. Vigneron, John Kurhanewicz
Journal: Cancer Research (2008)

An extraordinary new technique using hyperpolarized (13)C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-(13)C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 +/- 11, 74 +/- 17, and 154 +/- 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional (13)C spectroscopic imaging studies of prostate cancer patients.
Genetic and Molecular Aspects of 2,3,7,8-Tetra-Chlorodibenzo-P-Dioxin Action
Authors: J P Whitlock
Journal: The Annual Review of Pharmacology and Toxicology (1990)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More