tbuckley/cabot-search huggingface dataset:
Tamoxifen Resistance in Estrogen Receptor Positive (ER+) Breast Cancer Is Driven by Estrogen Receptor Negative (ER-) Cancer Stem-Like Cells.
Authors: C. O'Brien, S. Howell, J. Gee, A. Lykkesfeldt, R. Nicholson, R. Clarke
Journal: Cancer Research (2009)

Abstract Introduction: Intrinsic and acquired resistance to endocrine therapy significantly reduces survival rates of women with ER+ breast cancer. In the normal breast, multipotent stem cells are ER-. We hypothesised that tumourigenic breast cancer stem-like cells (CSCs) are ER- and therefore function independently of estrogen, representing a novel mechanism of resistance to endocrine therapy.Methods: Three ER+ cell lines, MCF-7, T47D and BT474 were assessed for ER expression by immunocytochemistry (ICC) in monolayer and after CSC enrichment. Putative CSC number was assessed by the non-adherent mammosphere (MS) assay, in the presence and absence of tamoxifen, and by Fluorescence Activated Cell Sorting (FACS) for the markers CD44+/CD24-/low/epithelial specific antigen(ESA)+. The effect of acquired Tamoxifen resistance on the CSC population of two independent Tamoxifen-resistant (TAM-R) MCF-7 variants, from Cardiff (TAM-RCARD) and Copenhagen (TAM-RCOP) was compared to parental, tamoxifen sensitive (TAM-S) controls. In the MS assay both the number and size of colonies were assessed.Results: A small sub-population of ER_ cells were demonstrated in MCF7 (6.1 ± 1.4%), T47D (6.8± 0.5) and BT474 (3.7±1.3) cells by ICC. However, the majority of putative breast CSCs (CD44+/CD24-/low/ESA-) in MCF7 cells were ER_ (73.2 ± 4.6 % p= 0.0007). There was a significant increase in the proportion of ER- cells in TAM-R cell lines (TAM-RCARD 11.6 ± 1.4% p=0.01 and TAM-RCOP 22 ± 4.8% p=0.02 respectively) compared to the parental TAM-S controls. Both TAM-R cell lines demonstrated increased mammosphere forming efficiency (MFE) compared to TAM-S cells (TAM-RCARD 4% vs. 2.5% p=0.03, and TAM-RCOP 8% vs. 3% p=0.007). The putative CSC population (CD44+/CD24-/low/ESA+) was enriched more than 2.5 fold in TAM-R compared to TAM-S parental controls. Compared with controls, the absolute MFE was not affected by Tamoxifen treatment, although mammospheres formed were significantly smaller.Conclusions: The majority of the putative CSC populations in ER+ breast cancer do not express ER. There is an increase in the proportion of putative ER- CSCs in TAM-R MCF7 cell lines. The reduction in MS size suggests that Tamoxifen targets transit amplifying cells but does not reduce the absolute number of CSC in ER+ breast cancers. These findings demonstrate a novel mechanism of endocrine resistance in ER+ breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5125.
Abstract 2806: A phase Ia/Ib trial of chemotherapy followed by infusions of activated T cells armed with OKT3 x trastuzumab bispecific antibody, IL-2 and GM-CSF for stage II/ III, Her2+ or Her2- high risk breast cancer (more than 10+ nodes)
Authors: Deepa B. Jagtap, Ritesh Rathore, Archana Thakur, Gerald Colvin, Nicola Kouttab, Abby Maizel, Abhinav Deol, Lawrence G. Lum
Journal: Cancer Research (2014)

Abstract Background: Anti-CD3 x anti-HER2Bi bispecific antibody (HER2Bi) targeted monoclonal antibody (mAb) activated T cells (ATC) exhibit anti-HER2 cytotoxicity, proliferate, and secrete immunokines upon tumor engagement. This study reports a phase I immunotherapy trial in 9 women with locally advanced breast cancer consisting of infusions of HER2Bi armed ATC (aATC) in combination with interleukin 2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) to evaluate safety, feasibility, time to progression (TTP), overall survival (OS), T cell trafficking, and immune responses. Methods: ATC were produced by stimulating peripheral blood mononuclear cells (PBMC) obtained by leukapheresis with anti-CD3 monoclonal antibody and expanding the ATC in IL-2. ATC were harvested, armed with HER2Bi and cryopreserved in aliqouts. Groups of 3 patients received 20, 40, 80 or 160 x 109 aATC per infusion twice a week for four weeks(Table 1). Results: Eight of 9 patients were ER positive, 2 of 9 were Her 2 overexpressing tumors. The median OS for all patients was 103.5 months (14.3 to 134.7months). Six of 9 patients are alive. Four out of the six patients have no evidence of disease and 2 patients relapsed (one at 77.27 months and the other at 104.67months). It was feasible to grow up to 160 x 109 ATC and both patients assigned to this dose level were able to reach it. There were no cell-based dose limiting toxicities. aATC persisted in the blood for at least a week. aATC infusions induce cellular anti-tumor responses and cytokine responses. Interpretation: Targeting Her2 positive and negative tumors induced cytotoxic anti-tumor responses, increases in Th1 cytokines and IL-12 serum levels, clinical responses that suggest aATC infusions provided a survival benefit. These results are being confirmed in a phase II trial for metastatic breast cancer. Table 1Planned doseActual Dose20Bill21.640Bill42.7540Bill37.640Bill42.480 Bill80.080Bill70.3580Bill96.0160Bill176.75160Bill160.0 Citation Format: Deepa B. Jagtap, Ritesh Rathore, Archana Thakur, Gerald Colvin, Nicola Kouttab, Abby Maizel, Abhinav Deol, Lawrence G. Lum. A phase Ia/Ib trial of chemotherapy followed by infusions of activated T cells armed with OKT3 x trastuzumab bispecific antibody, IL-2 and GM-CSF for stage II/ III, Her2+ or Her2- high risk breast cancer (more than 10+ nodes). [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 2806. doi:10.1158/1538-7445.AM2014-2806
Effectiveness of antimicrobial photodynamic therapy with a single treatment of RLP068/Cl in an experimental model of Staphylococcus aureus wound infection
Authors: O. Simonetti, O. Cirioni, F. Orlando, C. Alongi, G. Lucarini, C. Silvestri, A. Zizzi, L. Fantetti, G. Roncucci, A. Giacometti, A. Offidani, M. Provinciali
Journal: British Journal of Dermatology (2011)

Background Chronic leg ulceration is a common health problem. It is well known that a clinically relevant bacterial load in chronic cutaneous wounds interferes significantly with the normal process of healing. Staphylococcus aureus is the most important representative of the staphylococcal group which causes clinically relevant infections within immunocompetent patients. Objectives To investigate the efficacy of a single treatment of antimicrobial photodynamic therapy (APDT) with RLP068/Cl in a mouse model of a surgical wound infection induced with a methicillin‐resistant strain of S. aureus (MRSA). Methods Wounds, established through the panniculus carnosus of BALB/c and CD1 mice, were inoculated with 5 × 107 c.f.u. of MRSA. Mice were randomized into four groups respectively receiving no treatment, APDT with placebo, APDT with a new phthalocyanine derivative (RLP068/Cl) and intraperitoneal teicoplanin. Results On day 2 from infection, a strong reduction of bacterial counts (≈ 3 logs) was observed in mice treated with RLP068/Cl in comparison with infected untreated mice. On day 9 from infection, a comparable and significant (≈ 2 logs) reduction of bacterial counts was found in mice treated with RLP068/Cl or with teicoplanin. At this time, histological examinations revealed that wounds treated with RLP068/Cl showed a complete re‐epithelialization with a continuous epithelial lining. Conclusions The results of the in vivo study demonstrated that APDT with RLP068/Cl may be useful in the management of chronic infected wounds, accelerating the repair process through a significant bacterial inhibition.
A novel approach to prepare a liposomal irinotecan formulations that exhibit significant therapeutic activity in vivo
Authors: Euan Ramsay, Jehan Alnajim, Malathi Anantha, Awa Dicko, Pierrot Harvie, Lawrence D. Mayer, Marcel B. Bally, Paul Tardi
Journal: Cancer Research (2004)

639  Purpose: Liposomal formulations of camptothecins are proving to be of clinical interest for several reasons including the potential of the formulations to protect the active form of the drug. Camptothecins possess an α-hydroxy-δ-lactone ring which undergoes reversible hydrolysis at physiological pH (pH ∼ 7) to an open ring-carboxylate form. The closed α-lactone ring appears to be structurally important for both passive diffusion of drugs into cancer cells and successful interaction with the topoisomerase I target. We have characterized a method for preparing liposomal formulations of irinotecan (CPT-11) that relies on interactions with an encapsulated transition metal. Methods: Liposomes were prepared in various salt solutions containing copper, zinc, manganese, and cobalt. The outside buffers were exchanged in order to create a metal ion gradient and the loading of CPT-11 in response to the encapsulated metal was determined. The role of pH and temperature in defining the loading rates of CPT-11 was assessed. HPLC and fluorescent spectroscopic methods were used to assess the chemical stability of CPT-11 following encapsulation. The therapeutic activity of CPT-11 encapsulated into DSPC/Chol liposomes using this method was determined using a murine LS180 (human colorectal cell line) xenograft model. Results: Using encapsulated unbuffered (pH3.5) transition metal salt solutions, CPT-11 accumulated (incubation temperature 50°C) to levels of 0.2 drug-to-lipid (mol:mol) in liposomes with encapsulated CuSO4 and ZnSO4. The loading efficiencies were >90%. These studies were repeated using an encapsulated buffered (pH7.5) CuSO4 solution. CPT-11 accumulated to levels of 0.2 drug-to-lipid (mol:mol) in liposomes with encapsulated CuSO4. The rate of CPT-11 loading into CuSO4 (pH7.5) containing liposomes was slower when the external pH was reduced to 6.5, however if the incubation temperature was increased to 60°C the rate of loading increased. Formulations exhibiting 0.3 drug-to-lipid ratios could be prepared using this technique and at this ratio the loading efficiency was still >90%. Studies indicated that CPT-11 loading into the liposomes occurred only when CPT-11 was in the closed α-lactone ring form. The resulting liposomal formulation exhibited substantial activity when used to treat mice bearing established LS180 tumours. Conclusion: A stable and therapeutically effective liposomal formulation of CPT-11 was prepared using a method which relied on the presence of an encapsulated transition metal to promote drug uptake.
Decreased Bacterial Diversity Characterizes the Altered Gut Microbiota in Patients With Psoriatic Arthritis, Resembling Dysbiosis in Inflammatory Bowel Disease
Authors: Jose U. Scher, Carles Ubeda, Alejandro Artacho, Mukundan Attur, Sandrine Isaac, Soumya M. Reddy, Shoshana Marmon, Andrea Neimann, Samuel Brusca, Tejas Patel, Julia Manasson, Eric G. Pamer, Dan R. Littman, Steven B. Abramson
Journal: Arthritis & Rheumatology (2014)

Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never‐treated, recent‐onset psoriatic arthritis (PsA). Methods High‐throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. Results The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia , Ruminococcus , and Pseudobutyrivibrio . Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. Conclusion Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis–PsA pathogenesis and the associated immune response merits further study.
A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation
Authors: Karine Merienne, Sylvie Jacquot, Solange Pannetier, Maria Zeniou, Agnes Bankier, Jozef Gecz, Jean-Louis Mandel, John Mulley, Paolo Sassone-Corsi, André Hanauer
Journal: Nature Genetics (1999)
Abstract 2640: Clinical Characteristics and Risk Stratification in Symptomatic and Asymptomatic Patients with Brugada Syndrome - Multi-center Study in Japan-
Authors: Masahiko Takagi, Yasuhiro Yokoyama, Kazutaka Aonuma, Naohiko Aihara, Masayasu Hiraoka
Journal: Circulation (2007)

Background Neither the clinical characteristics nor risk stratification of symptomatic and asymptomatic patients with Brugada syndrome have been clearly determined. We compared clinical and ECG characteristics of symptomatic and asymptomatic patients with Brugada syndrome to identify new markers for distinguishing high- from low-risk patients. Methods A total of 216 consecutive individuals with Brugada syndrome (mean age 52±14 years, 197 males) were enrolled in the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS). Clinical and ECG characteristics were compared among 3 groups of patients: VF group; patients with aborted sudden death and documented VF (N=34), Syncope (Sy) group; patients with syncope without documented VF (N=70), and Asymptomatic (As) group; subjects without symptoms (N=112). Comparisons were made among the 3 groups as well as between the symptomatic (VF/Sy) and asymptomatic (As) groups. Short-term prognosis was also compared among the 3 groups, and between the VF/Sy and As groups. Results 1) Clinical characteristics: incidence of past history of AF was significantly higher in the VF and Sy groups than in the AS group (26, 26, and 12 %, respectively; [p=0.04]), though no other clinical parameters differed among the groups. 2) On resting 12-lead ECG, r-J interval (interval from QRS onset to J point) in lead V2 and QRS duration in lead V6 were highest in the VF group (104, 98, and 92 msec in V2 [p&lt;0.001]; 106, 103, and 94 msec in V6 [p&lt;0.0001], respectively, VF vs. Sy vs. As). 3) Positive late potential and inducibility of VF by EPS did not differ in incidence among the 3 groups. 4) Clinical follow-up: during a mean follow-up of 36±16 months, incidence of cardiac events (sudden death and/or VF) was higher in the VF/Sy groups than in the As group (29, 8, and 0 %, respectively [p&lt;0.001]). Multivariate analysis showed that the frequencies of r-J interval ≥ 90 msec in lead V2 and QRS duration ≥ 90 msec in lead V6 were significantly higher in patients with cardiac events (p=0.02, 0.02, respectively). Conclusions In symptomatic patients, prolonged ventricular depolarization in precordial leads of the ECG was prominent in the VF group, and this sign can be used to distinguish high- from low-risk patients with Brugada syndrome.
6-month follow-up in patients with advanced upper lobe predominant heterogeneous emphysema treated with endobronchial lung sealant therapy
Authors: Felix Herth, Ralf Eberhardt, Arschang Valipour, Franz Stanzel, Reiner Bonnet, Juergen Behr, Charles Marquette, Mordechai Kramer
Journal: European Respiratory Journal (2011)

Objective(s): Responses to AeriSeal® Emphysematous Lung Sealant System (ELS) therapy in patients with advanced upper lobe predominant heterogeneous (ULP) emphysema are summarized out to 6 months of follow-up.

Methods: 14 patients with ULP emphysema received ELS treatment in a multi-center study conducted at 8 sites across Europe and Israel. Ten (10) of these patients underwent a second treatment session after 12 weeks in the contralateral upper lobe to complete bilateral therapy. Pulmonary function, functional capacity, and quality of life assessments were performed at 3 and 6 months following treatment.

Results: Upper lobe ELS therapy in this cohort (8 male, age 63±6 yrs) was associated with improvements in pulmonary function, functional capacity, and quality of life. Three (3) and 6 month improvements in FEV1 (+17.4±33.1%; 20.3±33.3%), FVC (11.3±24.7%; 12.3±24.2%), RV/TLC ratio (-7.5±11.1%; -6.2±7.4%), MRCD (-0.3±0.83U; -0.4±0.77U), 6MWT (+22.4±105.9m; +31.6±80.6m), and SGRQ (-9.5±11.3U; -6.3±9.6U) were reported. Clinically significant improvements in spirometry were observed in 9 of 14 patients at 6 month follow-up. Physiological responses were best in those patients (n=10) who received bilateral upper lobe split dose therapy (ΔFEV1 = +24.8±36.8%; ΔFVC = +17.6±25.6%).

Conclusions: ELS therapy in patients with advanced ULP emphysema improves lung function, functional capacity and quality of life out to at least 6 months. Improvements in spirometry following bilateral upper lobe therapy can be equivalent to those observed following lung volume reduction surgery.
Persistent Activation of Nuclear Factor Kappa-B Signaling Pathway in Patients With Unstable Angina and Elevated Levels of C-Reactive Protein
Authors: Giovanna Liuzzo, Matteo Santamaria, Luigi M. Biasucci, Michela Narducci, Valeria Colafrancesco, Annalisa Porto, Salvatore Brugaletta, Michela Pinnelli, Vittoria Rizzello, Attilio Maseri, Filippo Crea
Journal: Journal of the American College of Cardiology (2006)
Helping patients in hospital to quit smoking
Authors: R. West
Journal: BMJ (2002)

Papers p 87 

This issue reports a study that nicely encapsulates the problems facing hospitals who want to encourage and help their patients to stop smoking (p 87).1 The study focuses on inpatients with cardiac disorders who want to stop smoking and examines whether a brief intervention (averaging 34 minutes) delivered on the ward by nurses would help them stop. It finds no effect at six weeks and at follow up after one year. This mirrors results with other patient groups. Most notably two large randomised controlled trials, one in the United Kingdom and one in Denmark, have found that a brief intervention by midwives failed to improve pregnant smokers' chances of stopping. 2 3 All three studies also found that busy staff had considerable difficulty finding time to undertake the counselling. How can one square this with claims that brief advice from healthcare professionals leads patients to stop smoking and that …
Textbook of Clinical Neuropharmacology and Therapeutics
Authors: Harold L. Klawans, Christopher G. Goetz, Caroline M. Tanner
Journal: Annals of Internal Medicine (1992)

nomena that Pavlovian conditioning is not able to explain.An important question that the author raises is whether or not the opponent-process states are predictable.He is convinced that they are and analyzes the process of food intake and obesity following the logic of opponent-process theory.Neurobiology ofLearning, Emotion, and Affect is a well organ-
CONVULSIVE STATES AND MULTIPLE SCLEROSIS: REPORT OF A CASE
Authors: P G HAMLIN
Journal: Annals of Internal Medicine (1955)

Case Reports1 January 1955CONVULSIVE STATES AND MULTIPLE SCLEROSIS: REPORT OF A CASEPERCY G. HAMLIN, M.D., F.A.C.P.PERCY G. HAMLIN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-42-1-201 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptConvulsive seizures—focal, Jacksonian and generalized—occurring during the course of or symptomatologically antecedent to multiple sclerosis have been but rarely recorded in medical literature.Kinnier Wilson,8however, stated in 1940 that it was important to realize that multiple sclerosis must be numbered among the causes of epilepsy. He was able at that time to number eight cases collected from the literature and to add seven of his own and one of Patrick's (Journal of Nervous and Mental Diseases47, 1918) for a total of 16 recorded cases. Störring5in 1940 reported an additional 13 cases of his own observed among 205...Bibliography1. BronischRauch FWHJ: Zur Pathogenese der epileptischen Anfälle bei multipler Sklerose, Deutsch. Ztschr. Nervenh. 158: 322-347, 1947. CrossrefGoogle Scholar2. House of Representatives 82nd Congress: HR 3205, Hearing Before Subcommittee on Veterans Affairs, Government Printing Office, Washington, D. C., 1951. Google Scholar3. Nielsen JM: Multiple sclerosis (disseminated sclerosis), Clinics 4: 416-447 (Aug.) 1945. Google Scholar4. Penfield W: Epilepsy and cerebral localization, 1941, Charles C. Thomas, Springfield, Illinois. Google Scholar5. Störring GE: Epilepsie und multiple Sklerose: Zugleich ein Beitrag zur differential Diagnose der Epilepsie, Arch. f. Psychiat. 112: 45-75, 1940. CrossrefGoogle Scholar6. Von StorchLawyerHarris TJTAH: Colloidal gold reaction in multiple sclerosis, Arch. Neurol. and Psychiat. 64: 668-675 (Nov.) 1950. CrossrefGoogle Scholar7. WilliamsNosikHunter GHWAJA: Convulsions as manifestation of multiple sclerosis, J. A. M. A. 150: 990-992 (Nov. 8) 1952. CrossrefMedlineGoogle Scholar8. Kinnier Wilson SA: Neurology, edited by A. Ninian Bruce, 1940, Edwin Arnold and Company, London. Google Scholar9. ZimmermannNetsky HMMG: The pathology of multiple sclerosis, in Proceedings of the Association for Research in Nervous and Mental Diseases, 1950, Williams and Wilkins Company, Baltimore. Google Scholar10. Patrick HT: Jacksonian fits in multiple sclerosis, J. Nerv. and Ment. Dis. 47: 176, 1918. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Canoga Park, California*Received for publication March 26, 1954. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEpilepsy with Multiple SclerosisDie cerebralen Anf�lle bei der Multiplen Sklerose 1 January 1955Volume 42, Issue 1Page: 201-205KeywordsEpilepsyMultiple sclerosis ePublished: 1 December 2008 Issue Published: 1 January 1955 PDF downloadLoading ...
Attending Physician Performance Measure Scores and Resident Physicians’ Ordering Practices
Authors: Brandyn D. Lau, Michael B. Streiff, Peter J. Pronovost, Adil H. Haider, David T. Efron, Elliott R. Haut
Journal: JAMA Surgery (2015)

This study reports that, at academic medical centers, many common process measures are entirely dependent on resident physicians with minimal direct, real-time oversight or feedback from attending physicians.
Beyond big and small mice: applications of mouse molecular genetics in endocrinologyTransgenic Models in Endocrinology edited by Maria Castro. Kluwer, 2001. EUR 210.00/US$189.00/GB£130.00 (xii+265 pages) ISBN 0 7923 7344 8 Transgenics in Endocrinology edited by Martin M. Matzuk, Chester W. Brown and T. Rajendra Kumar. Humana Press, 2001. US$175.00 (x+485 pages) ISBN 0 896 03764 9
Authors: Lori T. Raetzman, Sally A. Camper
Journal: Trends in Endocrinology and Metabolism (2003)