tbuckley/cabot-search huggingface dataset:
Abstract 2564: No Late and no Very Late Stent Thrombosis with a Drug-Eluting Stent of the Second Generation: 2 Years Results from the Randomized NOBORI-I Trial
Authors: Sigmund Silber, Bernard Chevallier, Patricl Serruys, E. Garcia, Gregorio Maranon, Harry Suryapranata, Isala Klinieken
Journal: Circulation (2008)

Background: Late (after 30 days to 1 year) and very late (after 1 year) stent thrombosis is a continuous concern for drug-eluting stents (DES) of the first generation. These stents are characterized by their durable polymer and a ,,360 degree“ elution of the antiproliferative drug not only into the vessel wall, but also into the blood stream. Therefore, the second generation Nobori stent was developed with a biodegradable polymer and a drug elution restricted only to the vessel wall (abluminal coating). The drug, Biolimus A9, is a potent antiproliferative and antiinflammatory Limus derivative. Methods: The NOBORI-I trial was a prospective randomized study designed to compare the Nobori stent with the Taxus stent (2:1) in pats with single de-novo native coronary lesions, a vessel diameter of 2.5–3.5 mm and a lesion length below 25 mm. Predilatation was required. The primary endpoint was in-stent late lumen loss (LL) at 9 months. The study was designed as a noninferiority trial. 363 pats were enrolled in 29 sites in Europe, Asia and Australia. Clopidogrel (in addition to ASA) was recommended for at least 6 months. Results: With an in-stent LL of 0.12 mm in the Nobori and 0.33 mm in the Taxus group (p &lt;0.001) the primary endpoint was reached, with a significant result also for superiority. The results for late and very late stent thrombosis are depicted in the table . Dual antiplatelet therapy was present at one year in 52% of the pats in the Nobori and in 55% of the pats in the Taxus group. After 2 years, it was maintained in 25% of the Nobori and in 20% of the Taxus pats. Conclusions: As compared to a DES of the first generation with a durable polymer and circumferential drug release, the second generation Nobori stent with its biodegradable polymer and a drug-elution restricted to the vessel wall seems to be safer. Due to the limited power of this study regarding safety, higher number of patients are needed to corrobarate these promising findings.
Genome Editing of the Germline: Broadening the Discussion
Authors: Matthew H Porteus, Christina T Dann
Journal: Molecular Therapy (2015)

Genome editing that results in humans with precisely modified germ cells may never become practical. Nonetheless, the implications are great enough that we strongly support the idea of starting the conversation now, providing time for a broad consensus to be developed. We are confident that if diverse voices are heard, a consensus can be reached on a strategy in which societal mores are respected, the desires of parents are integrated, and the health of future generations is maximized.
Extracellular matrix and breast cancer cells' response to trastuzumab: The role of glycosaminoglycans, heparanases, and syndecan-1.
Authors: Maria Aparecida Silva Pinhal, Eloah Rabello Suarez, Helena Bonciani Nader, Auro Del Giglio
Journal: Journal of Clinical Oncology (2012)

10568 Background: Trastuzumab is an antibody anti-epidermal growth factor 2 receptor (HER2), which improves disease-free and overall survival in HER2 positive breast cancer. Nevertheless, many patients become resistant to this treatment. Heparanase (HPSE) is an enzyme that is responsible for removal of heparan sulfate (HS) chains from proteoglycans, generating free oligosaccharides that modulate many physiopathological functions, including tumor developing. We have analyzed whether some extracellular matrix components influence trastuzumab efficacy. Methods: Heparanase-1 (HPSE-1) overexpression effect was analyzed using MCF7 cells stable transfected with HPSE-1 cDNA (MCF7-HPSE-1). HPSE-1, HPSE-2, Syndecan-1 (Syn-1) and HER2 expression, HPSE-1 activity and cell viability were evaluated in different breast cancer cells treated or not with trastuzumab. The glycosaminoglycans synthesis and shedding were also evaluated. Trastuzumab and HS binding were analyzed by confocal microscopy and Fluorescence Resonance Energy Transfer (FRET). Results: MCF7 transfected with HPSE-1 cDNA becomes completely resistant to trastuzumab. HS affinity by Trastuzumab was then tested, showing that they bind in high levels and this binding is necessary to antibody activity. In MCF7 cells, trastuzumab decreases HPSE-1, HPSE-2, HER2 and Syn-1 mRNA expression, while in MCF7-HPSE-1 the antibody increases the expression of these molecules. Conclusions: Our results have demonstrated that an ideal concentration of HS in cell surface, regulated by trastuzumab, is necessary to its action, beyond HER2 high levels. High HS concentration at cell surface enhances the antibody amount disposable to interact with HER2 in cell surface, determining breast cancer cells susceptibility to trastuzumab. These new insights could be useful when devising strategies for overcoming trastuzumab resistance in HER2 positive cancers. Supported by FAPESP, CNPq, CAPES.
The Parathyroid Glands and Metabolic Bone Disease: Selected Studies
Authors: Fuller Albright, Edward C. Reifenstein
Journal: JAMA (1949)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 5987: Long-Term Efficacy and Safety of Sirolimus-Eluting Versus Bare-Metal Stents for On- and Off-Label Indications
Authors: Marcin R Dada, Francis J Kiernan, Deborah J Murphy, Jill Cloutier, Athanasios Kapetanopoulos, Bhupinder Singh, Rameez Sayyed, Jeffrey F Mather, Roger A Mennett, Anuj R Shah, Raymond G McKay
Journal: Circulation (2008)

BACKGROUND: Although previous data suggest persistent clinical benefit of sirolimus-eluting stents (SES) in reducing target vessel revascularization without an increase in myocardial infarction (MI), cumulative stent thrombosis and mortality, the long-term safety and efficacy of CYPHER stent use in routine clinical practice, including off-label stent implantation, remains uncertain. METHODS: We examined clinical characteristics, angiographic findings, in hospital and long-term clinical outcomes in 3572 patients of whom 2,550 were treated with SES, and 1,022 who were treated with bare metal or heparin-coated stents (BMS). The study groups included 1,058 SES patients (41.5%) and 488 BMS patients (47.7%) with off-label indications, including acute MI, multivessel percutaneous coronary intervention, saphenous vein grafts and complex lesion morphology. A propensity-score method was utilized to adjust for differences in baseline characteristics. Patients were followed for up to 5 years for the occurrence of all-cause mortality, MI and repeat target vessel revascularization. RESULTS: Compared to the BMS patients, the SES group patients demonstrated significantly improved event-free survival with respect to all-cause mortality (RR, 1.39; 95% CI, 1.07 to 1.80, p=0.014) and repeat target vessel revascularization (RR, 2.72; 95% CI, 1.99 to 3.73, p&lt;0.001) during the follow-up period, with no significant difference in the incidence of MI. A landmark analysis, examining composite adverse events occurring six months after stent implantation in the two study groups, demonstrated no increased late hazard associated with SES use (relative risk, 1.08; 95% CI, 0.80 to 1.46). CONCLUSIONS : Use of SES in routine clinical practice, including off-label indications, is associated with improved long-term mortality, reduced need for repeat target vessel revascularization and no increase in MI compared to BMS.
Inhibition of <i>O</i><sup>6</sup>-methylguanine DNA methyltransferase (MGMT) in solid tumors by lomeguatrib
Authors: A. Sabharwal, A. J. Watson, S. Bojanic, R. S. Kerr, Z. Soonawalla, H. Leung, A. King, A. Miller, G. P. Margison, M. R. Middleton
Journal: Journal of Clinical Oncology (2008)

3597 Background: MGMT is implicated in tumor resistance to O6-alkylating agents, since the protein repairs DNA damage before replication results in cell death. Lomeguatrib (LM) is an orally bioavailable pseudosubstrate for MGMT that inactivates the protein through transfer of a boromthenyl group to the active site cysteine. De novo synthesis is required to restore cellular MGMT levels. We determined the dose of LM needed reliably to deplete MGMT in 3 tumor types, to inform future combination studies with methylating agents. Methods: Patients due to undergo surgery for prostate, colorectal or primary CNS cancers were invited to take part. They were dosed with LM PO 6 to 18 hours before surgery, and a portion of the tumor specimen retained for assessment of total and active MGMT. Active MGMT was assessed by transfer of tritium from methylated DNA to the protein fraction, and total MGMT by ELISA. 3 patient cohort dose escalations were used, with expansion to 6 patients where total depletion was encountered. Dose levels were 20, 40, 80, 120, and 160 mg. Results: LM was well tolerated and depleted MGMT in all 3 tumor types (table 1). Prostate cancers had the highest levels of MGMT (550 Fmol/mg protein) but were the most readily depleted tumour type. CNS tumours required more LM to achieve 100% depletion. Conclusions: Lomeguatrib depletes MGMT in prostate, colorectal and CNS cancers after single oral doses of 120 mg, 120 mg, and 160 mg respectively. Mean MGMT depletion (%) with a single LM dose Dose Level (mg) Prostate Cancer Colorectal Cancer Glioblastoma 20 81.7 44.7 40 96.8 61 46 80 98.3 96.5 57 120 99.5 97.7 73.4 160 100 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cancer Research UK
Eradication of prostate cancer by immunotherapy using the most potent macrophage activating factor, GcMAF
Authors: Nobuto Yamamoto, Masumi Ueda, Kazuya Hashinaka, Nobuyuki Yamamoto, Charles Benson
Journal: Cancer Research (2007)

1869  Highly activated macrophages are tumoricidal. Inflammation-derived macrophage activation is the principal macrophage activation process that requires serum vitamin D-binding protein (known as Gc protein) and participation of B and T lymphocytes. A trisaccharide composed of N-acetylgalactosamine with dibranched galactose and sialic acid termini at 420 threonine residue of Gc protein is hydrolyzed by the inducible s-galactosidase (Bgl) of inflammation-primed B cells and the Neu-1 sialidase of T cells to yield the macrophage activating factor (MAF). Thus, Gc protein is the precursor for the principal MAF. However, the MAF precursor activity of Gc protein of cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells but not from healthy cells. Thus, serum Nagalase activity is proportional to tumor burden and serves as a prognostic index. Exogenously given macrophage activating factor can bypass deglycosylated serum Gc protein and directly acts on macrophages for activation. Stepwise treatment of highly purified Gc protein with immobilized s-galactosidase and sialidase generated the most potent macrophage activating factor (GcMAF) ever discovered which produces no side effect in humans. Administration of 100 ng GcMAF per human results in the maximal activation of systemic macrophages, which develop enormous variation of receptors that recognize a variety of abnormalities, i.e., tumor associated antigens, in cancerous cell surface. When sixteen nonanemic prostate cancer patients were treated with 14-25 weekly administrations of 100 ng GcMAF (intramuscularly once a week), all cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of tumors. During two years after GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence. Poorly differentiated (termed undifferentiated) cancer cells should have more abnormality in cell surface than moderately or immediate differentiated (differentiated for short) cancer cells. Since the activated macrophages efficiently recognize and kill cancer cells having more abnormality, the activated macrophages cure patients with undifferentiated tumors more rapidly than those with differentiated tumors. However, the serum Nagalase activity of the majority of patients decreased rapidly in the first few weeks (up to 4 weeks) and followed by slow decrease during remaining therapeutic period (10-20 weeks). The result suggests that undifferentiated cells were mixed with differentiated cells in same tumor. These mixed cell population appeared to be developed by differentiation during growth of the undifferentiated tumor cells.
Ultrastructural Aspects of the Liver and Its Disorders.
Authors: Kyūichi Tanikawa
Journal: Annals of Internal Medicine (1970)

chapters on motility.Diet, and psycho- logical aspects, are not considered, and the liver is allotted little more than two chapters.The book has to compete with review articles which appear regularly in the journals.The editors have sought to provide a balance of topics within gastro- enterology, and, as a balanced and thoughtful text, it is the best available.It is a book that will be read with interest by gastroenterologists,
Megestrol acetate after aromatase inhibitor failure in metastatic breast cancer
Authors: L. P. Branco, R. Dienstmann, J. Bines
Journal: Journal of Clinical Oncology (2006)

10572 Background: As aromatase inhibitors (AI) are now an essential component of the adjuvant hormonal treatment in breast cancer, it is important to define strategies after progression. Progestational agents have significant activity in endocrine-responsive breast cancer. This is the first report of megestrol acetate (MA) after AI failure. Methods: We have retrospectively reviewed the charts of all patients treated with MA for the last 2 years at the Instituto Nacional de Câncer, in Brazil. All the patients were postmenopausal and had metastatic breast cancer. The treatment sequence was as follows: tamoxifen ⋄ AI ⋄ MA. MA was given at a dose of 160 mg PO daily. Results: A total of 27 postmenopausal patients were treated between December 2003 and December 2005. Median age was 71 years (37–93). Seven patients had visceral metastases and 20 had bone, soft tissue or pleural disease. Eight patients are still on treatment. Median time to disease progression was 16 weeks (4–81), with no difference between those with or without visceral metastases: 17 and 16 weeks, respectively. Treatment was well tolerated and no patient discontinued therapy due to toxicity. There was no report of venous thromboembolism. Conclusions: Despite the limitations of a retrospective analysis, our results compare favorably with exemestane and high-dose estrogens in a similar setting. These agents have been studied in phase II trials (Lonning PE. JCO 18: 2234, 2000 and BCRT 67: 111, 2001) and showed time to progression of 15 and 18 weeks, respectively. A prospective trial of MA after AI failure is warranted. No significant financial relationships to disclose.
Abstract 15184: MicroRNA Expression Profiling in Circulating Microparticles of Patients with Acute Coronary Sindrome
Authors: Margherita Marcantoni, Luigi M Biasucci, Luca Di Vito, Gianluigi De Maria, Ilaria Dato, Giuliana Di Rocco, Massimo Gustapane, Anna Severino, Italo Porto, Filippo Crea
Journal: Circulation (2011)

AIMS: microRNA (miRNA) are small non-coding RNA regulating gene expression on the post-transcriptional level by binding to the target mRNA. Recent studies have shown that circulating microparticles...
Inotuzumab Ozogamicin In Combination With Low-Intensity Chemotherapy (Mini-hyper-CVD) As Frontline Therapy For Older Patients (≥60 years) With Acute Lymphoblastic Leukemia (ALL)
Authors: Nitin Jain, Susan O'Brien, Deborah A. Thomas, Elias Jabbour, Stefan Faderl, Farhad Ravandi, Gautam Borthakur, Sergernne York, Rebecca Garris, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Blood (2013)
Data Collection Forms in Clinical Trials
Authors: Bert Spilker, John Schoenfelder
Journal: Annals of Internal Medicine (1991)

Part 1 Creating data collection forms: an overall approach - building a library of forms types of forms choosing modules and designing forms preparing the data collection form package reproducing and assembling forms remote date entry forms data processing and storage of completed forms selected issues. Part 2 Examples of data collection forms: background of a clinical trial instructions for completing data collection forms times and events schedules demographics medical history specific types of medical histories medication history inclusion and exclusion criteria. Part 3 Physical and other examinations: physical examinations vital signs neurological and ophthalmological examinations psychological and psychiatric tests. Part 4 Other specialized physical examinations, laboratory tests and evaluations: clinical chemistry and hematology tests radiology and pathology reports electrocardiograms urine, microbiology, virology, neurological, immunological and endocrinological tests pulmonary function studies other laboratory tests adverse experiences. Part 5 Medicines and assays of biological levels - dosing and dispensing: records concomitant medications pharmacokinetic samples to assay. Part 6 Efficacy: evaluations compliance patient diaries. Part 7 Patient termination and miscellaneous forms: termination and premature patient discontinuation global clinical impressions additional and unscheduled visits comment log and investigator verification.
Memory reconsolidation keeps track of emotional changes, but what will explain the actual “processing”?
Authors: Antonio Pascual-Leone, Juan Pascual-Leone
Journal: Behavioral and Brain Sciences (2015)

Abstract We question memory reconsolidation and emotional arousal as sufficient determinants of therapeutic change. Generating new feelings and meanings must be contrasted with activating and stabilizing the evolving memories that reflect those novel experiences. Some therapeutic changes are not attributable to a memory model alone. “Emotional processing” is also needed and is often an undeclared form of complex executive problem solving.
Costs of absenteeism and short-term disability associated with breast cancer to U.S. employers.
Authors: S. D. Sullivan, A. Z. Fu, M. Jhaveri, N. P. Christiansen
Journal: Journal of Clinical Oncology (2010)

6048 Background: Few data exist on the impact of breast cancer (BC) on indirect costs associated with absenteeism and short-term disability (STD) to U.S. employers. This study was undertaken to provide such empirical data in the U.S. population. Methods: This was a retrospective matched cohort study design using a large claims database from a U.S. national commercially-insured population between January 2003 and December 2007. Women aged ≥ 18 were selected with ≥ 2 BC diagnosis (ICD-9 code: 174.xx) on different dates within 90 days, ensuring that the diagnosis code represented actual disease condition instead of that for a regular screening. The date of the first BC diagnosis was served as the index date for case cohort. The control cohort (without BC) was selected with 1:1 matching to cases based on index date (same year and month), age (5 year range), region, employer, and health insurance type. Both case and control cohorts were required to have continuous enrollment for at least 6 months prior to and 12 months after the index date. Indirect cost was measured by days absent from work and STD days, with daily wage assigned using the average Bureau of Labor Statistics wages matched by age. Two-part model was applied to evaluate the 1-year post-index indirect cost difference between cases and controls with the adjustment of demographics, comorbid conditions, and pre-index total health care cost. Results: Based on the inclusion criteria, 856 and 2,668 patients were selected for absenteeism and STD outcomes, respectively, with mean age of 49 and 50 years. The days of absenteeism were 35 and 21 and STD days were 51 and 5 for cases and controls, respectively, within the post-index year (both p < 0.001). Two-part models predicts that the adjusted incremental costs for absenteeism and STD were $1,911 and $6,157 (p < 0.001) per BC patient per year. Conclusions: This study demonstrated that BC is associated with a large amount of indirect cost loss, which includes cost of absenteeism and, more importantly, cost of STD to the employer within the first year of diagnosis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Benefit from adjuvant anthracyclines according to hormone receptor status
Authors: G. Atalay Basaran, D. Cabuk, M. Teomete, B. Gulluoglu, H. Kaya, F. Dane, P. F. Yumuk, N. S. Turhal
Journal: Journal of Clinical Oncology (2008)

11513 Background: Several trials have consistently reported that there is marked heterogeneity in the magnitude of chemotherapy benefit according to the level of hormone receptor expression. Methods: We reviewed the medical records of early breast cancer patients with known receptor status who had anthracycline based adjuvant (CA, CE, CEF or CAF) CT between 1999–2006 in our institution. We recorded the clinical/pathologic characteristics of ER/PR+/+ and ER/PR−/− tumors (tms), analyzed survival outcome according to receptor status. Results: 258 of 318 tumors were both ER,PR positive. In the receptor positive (RP) subset % 40 patients were postmenopausal, %57 had nod positive disease, % 27 had breast conserving surgery (BCS). Her-2 was 2+/3+ in % 12 tms and %67/20 tms were grade 2/3 respectively. In the receptor negative (RN) subset (n:60) all patients were postmenopausal, %48 had nod positive disease, % 24 had BCS. Her-2 was 2+/3+ in % 24 tumors, %60 were triple negative and %41 /55 pts had grade 2/3 tumors respectively. 8-year overall survivals were %88 and %89 in the RP and RN subsets respectively and the curves did not diverge over time. 3-year and 8-year DFS were %88 and %64 in the RP group. 3-year and 8-year DFS were %81 and %66 in the RN group. The DFS curves converge at fourth year and then slightly diverge. Conclusions: Patients with ER/PR positive tms had fewer relapses than those with RN tms in the first four years following anthracycline based chemotherapy. Thereafter the difference in relapse patterns between RP and RN groups disappear. More effective, possibly targeted, treatment strategies are needed for RN tms and optimization of endocrine therapy is crucial in RP group. No significant financial relationships to disclose.
Abstract 16424: A Critical Role of Poly-ADP Ribose Polymerase 1 (PARP-1) in Human Pulmonary Arterial Hypertension
Authors: Audrey Courboulin, Jana Krietsch, Yan Coulombe, Guy Poirier, Jean Yves Masson, Sébastien Bonnet
Journal: Circulation (2011)

Background: Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by vascular lesions and obstructions of the distal pulmonary arteries (PA). This phenotype is associate...