tbuckley/cabot-search huggingface dataset:
Pilot study with pegylated liposomal doxorubicin (PLD) and docetaxel as first-line treatment in patients with metastatic breast cancer (MBC)
Authors: J. R. Mel, M. Ramos, J. Cueva, J. Castellanos, C. Almanza
Journal: Journal of Clinical Oncology (2009)

e12002 Background: Anthracyclines (AC) and taxanes are the most active cytotoxic agents for the treatment of MBC. The use of AC is limited by their acute toxicities and by their potential to cause cumulative cardiac damage. The development of alternative formulations of AC, such as pegylated liposomal doxorubicin (PLD) with lower toxicity may improve tolerability and efficacy of AC based regimens. This study has been conducted to determine the efficacy and toxicity profiles of docetaxel and PLD as first line treatment in patients (pts) with MBC. Methods: Pts ≥ 18 years with histologically confirmed breast cancer, advanced disease, PS ≥ 60%, LVEF&gt; 50%, adequate bone marrow, renal and hepatic function were included. No prior systemic therapy for MBC was allowed. Pts with brain metastases were excluded. Docetaxel 60 mg/m 2 iv followed by PLD 30 mg/m 2 iv day 1 every 3 weeks up to 6 cycles were given. Results: Thirty women with a median age of 64 years (40–81) were included. (76.7%) of pts were postmenopausal, Karnofsky PS 100 and 90 were 48% and 21% respectively, 86% of pts had ductal carcinoma. Most common sites of metastasis were lung (57%), liver (47%), and bone (43%). 20/30 (67%) of pts were pretreated, 15 (50%) pts with AC-containing regiment and 17 (57%) with radiotherapy. A total of 157 cycles (median 6, range 2–6) were administered. Median relative dose intensity was 90% for docetaxel and 88% for PLD. Over 28 pts assessable for response, overall response rate was 35.7% (95% CI: 18.0%-53.4%), all of them PR. With a median follow-up of 20.5 months, median time to progression was 8.1 months. Main grade 3 nonhaematological toxicities were PPE (27%), mucositis (27%), and asthenia (17%). No grade 4 nonhaematological toxicities were observed. Main grade 3/4 haematological toxicities were neutropenia (17%), leucopenia (10%), and thrombopenia (6.7%). 4 pts (13%) had febrile neutropenia. Conclusions: Docetaxel and PLD administered every 21 days as first-line treatment in MBC is an active schedule with an acceptable toxicity profile. No significant financial relationships to disclose.
Abstract 17567: Stanniocalcin-1 Induces A Novel Anti-Oxidant Pathway in Cardiomyocytes
Authors: Yanlin Wang, Dajun Liu, Luping Huang, Wei Wang, Xander H Wehrens, Tatiana Belousova, Maen Abdelrahim, Gabriel DiMattia, David Sheikh-Hamad
Journal: Circulation (2011)

Rationale: We have shown increased cardiac stanniocalcin-1 (STC1) in patients with idiopathic dilated cardiomyopathy. STC1 localizes to the inner mitochondrial, and transgenic overexpression of STC1 is associated with increased energy utilization. Objective: We examined the hypothesis that STC1 uncouples mitochondrial oxidative phosphorylation - to affect energy metabolism and superoxide generation in cardiomyocytes. Methods and Results: Compared to WT mouse heart, STC1 Tg heart displays 2-fold higher uncoupling protein 3 (UCP3) levels, 40% lower ATP levels, but similar activities of respiratory chain complexes I-IV. In cultured adult rat cardiomyocytes, recombinant hSTC1 is internalized by cultured rat cardiomyocytes and is targeted to the mitochondria within minutes; it induces UCP3, decreases mitochondrial membrane potential and suppresses baseline and ANG II-provoked superoxide generation. In freshly-isolated adult mouse cardiomyocytes, STC1 diminishes baseline and ANG II-induced superoxide generation equally in WT and gp91 phox -/- cardiomyocytes, suggesting gp91phox-independent mechanism of action. Baseline superoxide generation is higher in freshly-isolated adult UCP3 -/- mouse cardiomyocytes, compared to WT; and, treatment of UCP3 -/- cardiomyocytes with STC1 failed to suppress superoxide generation in the presence or absence of ANG II, suggesting that the effects of STC1 on superoxide generation are UCP3-mediated. Conclusion: STC1 activates a novel anti-oxidant pathway in cardiac myocytes through induction of UCP3; this pathway may play an important role in regulating reactive oxygen species in the heart under normal physiologic and pathophysiologic conditions, and ameliorate the deleterious effects of ANG II-mediated cardiac injury.
Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomised double blind placebo controlled trial
Authors: IngeborgBCKorthals-deBos, JanLHoving, MaurtisWvanTulder, MaureenPHRutten-vanMolken, HermanJAder, HenricaCWdeVet, BartWKoes, HindrikVondeling, LexMBouter, 王英民, 王福权
Journal: BMJ (2004)

目的：
评价血管紧张素转换酶抑制剂培哚普利对左室收缩功能障碍的老年患者6分钟行走距离及生活质量的影响。


环境：
老年日诊医院的医疗设施。


设计：
前瞻、双盲、安慰剂、对照试验。


受试者：
心脏超声判定的左室收缩功能障碍的66名患者（平均年龄81岁）。


干预：
滴定剂量的培哚普利或安慰剂治疗10周。


主要结局指标：
治疗10周后的6分钟行走距离，生活质量指标包括Minnesota心衰患者问卷和有36个项目的健康调查。


结果：
在左室收缩功能障碍的患者中，6分钟行走距离治疗组较安慰剂组明显增加（37.1m比-0.3m，P<0.001）。药物耐受性很好且无明显不良事件。


结论：
在由于左室收缩功能障碍导致心衰的老年患者中，培哚普利治疗可明显改善6分钟行走距离。
Abstract 12143: Association of Biomarkers with Pre-Existent Left Atrial Myocardial Scar in Atrial Fibrillation Patients Undergoing Catheter Ablation
Authors: Sanghamitra Mohanty, Prasant Mohanty, Luigi Di Biase, Rong Bai, Agnes Pump, Pasquale Santangeli, David Burkhardt, Shane Bailey, Joseph Gallinghouse, Rhodney Horton, Javier Sanchez, Jason Zagrodzky, Andrea Natale
Journal: Circulation (2011)

Introduction: Inflammatory mediators are known to play a key causative role in atrial structural remodeling that leads to myocardial scar formation. This study aims to examine possible association ...
Development, characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug
Authors: Poovi Ganesan, Rajpriyadarsini Soundararajan, Uma Shanmugam, Vinothini Ramu
Journal: Asian Journal of Pharmaceutical Sciences (2015)

The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists. Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates. The objective of this study was to improve solubility, release and comparability of dissolution of a poorly soluble drug using two different types of formulations (solid dispersions and microspheres). Hydrochlorothiazide was used as a model drug. The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose, hydroxypropyl methylcellulose in different drug-to-carrier ratios (1:1, 1:2 w:w). The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy, differential scanning calorimetry, percentage of practical yield, drug loading, surface morphology by scanning electron microscopy, optical microscopy and in-vitro release studies. The results showed no interaction between the drug and polymer, amorphous state of solid dispersions and microspheres, percentage yield of 42.53% to 78.10%, drug content of 99.60 % to 99.64%, good spherical appearance in formulation VI and significant increase in the dissolution rate.
Abstract 2215: Bleeding and Outcome in Acute Coronary Syndrome: Insights from Continuous ECG Monitoring in the INTERACT Trial
Authors: Andrew T Yan, Raymond T Yan, Mary Tan, Thao Huynh, David H Fitchett, Anatoly Langer, Shaun G Goodman
Journal: Circulation (2007)

Background: Bleeding is associated with adverse outcome in acute coronary syndromes (ACS). However, the precise pathophysiologic mechanisms have not been elucidated. Objective: To determine the rel...
Newly licensed drugs
Authors: L. Smeeth, J. Hippisley-Cox, J. A G Paris, R. Tiner
Journal: BMJ (1997)

Interferon beta in multiple sclerosis Reducing frequency and severity of relapses will be of great clinical benefitEditor-Richard G Richards's editorial on interferon beta in multiple sclerosis deals with the "clinical cost effectiveness" of the drug in the disease, but it lacks a fair balance, emphasising the cost effectiveness and minimising the clinical effectiveness of the drug. 1 Richards states that "the studies showed no evidence of any reduction in the more clinically relevant endpoint-the progression of disability, which should be the goal of treatment."This is his personal judgment and does not reflect the needs and wishes of patients with multiple sclerosis and their families.Multiple sclerosis is a distressing, humiliating, and often long drawn out disease with no cure.For this reason, quality of life, for the patients and their families, is paramount.A drug that can reduce the frequency and severity of relapses, whether or not it diminishes the progression of the disease, will be of great clinical benefit to many patients, improving their situation physically, psychologically, and socially.Surely happiness, feeling better, and increased health have great value.This is what many of us believe that the practice of our profession is about.
Detection of multiple accessory spleens in a patient with chronic idiopathic thrombocytopenia purpura.
Authors: HENTOK PHOM, BHARATHI DASAN J, RAJESH KASHYAP, ARUN MALHOTRA, VED CHOUDHRY, CHANDRASEKHAR BAL
Journal: Clinical Nuclear Medicine (2001)

Chronic idiopathic thrombocytopenia purpura is an immunologically mediated disorder resulting in disordered platelet kinetics and potentially life-threatening thrombocytopenia. Failure of medical therapy is an indication for splenectomy, and responses are seen in 70% of patients after this procedure. An important cause of relapse after splenectomy is the presence of accessory spleens. The authors describe a patient with chronic idiopathic thrombocytopenia purpura who had a relapse of symptoms 4.5 years after splenectomy. Tc-99m heat-denatured RBC planar and SPECT studies revealed the presence of multiple (more than 13) accessory spleens, but few of them were localized anatomically using computed tomography.
Augmentation of imatinib-induced cytotoxicity in human malignant glioma cells by suppression of autophagy
Authors: Takashi Shingu, Keishi Fujiwara, Yasuhiko Akiyama, Oliver Bogler, Kouzo Moritake, Naoki Shinojima, Yutaka Tamada, Tomohisa Yokoyama, Seiji Kondo
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2269 

Background: Malignant gliomas are the most common primary tumors of central nervous system. The prognosis of patients with malignant gliomas is poor in spite of current intensive therapy, including surgery, radiation, and chemotherapy. Therefore, we need to explore novel therapeutic modalities. Imatinib mesylate, a tyrosine kinase inhibitor of bcr-abl, c-abl, c-kit, and PDGFR    α and β, has recently been proved effective in the treatment of patients with several types of tumors such as Philadelphia chromosome positive leukemias. However, results of clinical trials for patients with recurrent malignant gliomas indicate that imatinib alone has insufficient activity. Moreover, the molecular mechanisms by which imatinib exhibits cytotoxicity against malignant glioma cells are not yet fully understood. Therefore, in this study, we determined the type of cell death caused by imatinib and explored the feasibility of sensitizing malignant glioma cells to imatinib. Materials and methods: Human malignant glioma cell lines U87-MG and U373-MG were treated with imatinib and assessed by cell viability assay, electron microscopy, and immunoblotting to determine the type of cell death. Because imatinib induced non-apoptotic cell death with autophagic features in tumor cells, autophagy was inhibited at different stages to assess the role of autophagy in cancer therapy: we used a class III phosphatidylinositol 3 kinase inhibitor 3-methyladenine (3-MA) or siRNA against Atg5 that inhibit autophagy at an early stage, or bafilomycin A1 or RTA203 that are vacuolar type H+-ATPase inhibitors and suppress autophagy at a late stage.    Results: Imatinib inhibited the viability of malignant glioma cells in a dose- dependent manner. Imatinib caused non-apoptotic autophagic cell death. When imatinib-induced autophagy was suppressed by 3-MA or siRNA against Atg5, the cytotoxicity of imatinib was attenuated. In contrast, bafilomycin A1 or RTA203 inhibited autophagy and enhanced the antitumor effect of imatinib through induction of apoptotic cell death in both tumor cells.    Conclusions: Imatinib causes non-apoptotic autophagy in malignant glioma cells. When autophagy was inhibited at a late stage, the cytotoxicity of imatinib was augmented by stimulation of apoptotic signal pathway. Our findings provide a potential strategy to sensitize malignant glioma cells to imatinib by inhibition of autophagy at a late stage.
Fibrin(ogen) stimulates breast, ovarian, and prostate cancer cell line invasiveness on the chick chorioallantoic membrane
Authors: Samantha Lacroix, Jolanta Stanisz, Kinga Smolen, David Wong, Mary Richardson, Gurmit Singh
Journal: Cancer Research (2004)

1821   The importance of hemostasis in tumor development is increasingly being recognized. Many tumor cells express procoagulant activity consistent with a putative role for coagulation in tumor cell migration, invasion, and metastasis. To explore and observe the affects of coagulation components, particularly fibrin(ogen), on tumor growth and invasion we utilized the chicken chorioallantoic membrane (CAM) model for the propagation of cancer cell lines grown in human plasma and fibrinogen clots. Cell lines of human breast cancer MCF-7, MDAMB231; ovarian cancer 2008, SKOV3; and prostate cancer PC3 were placed onto 9d CAMs (1x10 6  cells) in culture medium (CM), human fibrinogen clot (HFC), or human plasma clot (HPC) and incubated until 11d or 14d. CAMs were fixed in formalin; paraffin embedded and cross sections were prepared. Alterations in the CAM were monitored at 24-hour intervals with light microscopy and digital imaging. Cancer cell invasion into the CAM, angiogenesis, inflammation, and epithelial proliferation were evaluated and quantified on a + to 4+ basis from hematoxylin, eosin stained and immunohistochemically treated sections. Cancer cell colonies formed on all of the CAMs by 24h. In section at 48h cancer cells were observed within the parenchyma of the CAM, associated with damage to or removal of the epithelial layer. Cancer cell invasion increased when cells were grown in HPC (3+) compared to HFC (2+) and cells cultured in HFC displayed a higher level of invasion than CM (+/−) cells. There was limited evidence of angiogenesis, and this was similar among the growth conditions, but epithelial proliferation and inflammation demonstrated a similar trend to invasiveness. Breast cancer cell lines grown in HPC showed the greatest increase in invasive potential (3+), and as well were associated with the most enhanced angiogenesis, epithelial proliferation and inflammation compared to other growth conditions. Ovarian cancer cells displayed an intermediate response to culture in HPC (2+), and prostate cancer cells were the least responsive (+). A correlation between cancer cell invasiveness in the presence of HPC and to a lesser extent in HFC suggests a significant relationship among coagulation factors and metastasis. The increased potential of plasma clot compared to fibrinogen clot is consistent with the involvement of other coagulation components in tumor growth and metastasis. It is possible that a clot environment induces a more aggressive phenotype stimulating the production of matrix metalloproteinases and growth factors. The elucidation of the interplay of other coagulation factors, thrombin or tissue factor, and the distinct mechanisms of the interactions with tumor invasion and metastasis may impact cancer treatment.
Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice
Authors: Chava Rosen, Elias Shezen, Anna Aronovich, Yael Zlotnikov Klionsky, Yasmin Yaakov, Miri Assayag, Inbal Eti Biton, Orna Tal, Guy Shakhar, Herzel Ben-Hur, David Shneider, Zvi Vaknin, Oscar Sadan, Shmuel Evron, Enrique Freud, David Shoseyov, Michael Wilschanski, Neville Berkman, Willem E Fibbe, David Hagin, Carmit Hillel-Karniel, Irit Milman Krentsis, Esther Bachar-Lustig, Yair Reisner
Journal: Nature Medicine (2015)
Study ignored influence of parity on women's needs
Authors: S. Vause, M. Maresh, K. Khaled
Journal: BMJ (1996)

sample size would have given us 99.9% power to detect a difference in the rate of change in the scores obtained in the paired associate learning test of ¢ 0.1 point a year between treatments.Although it is desirable to test multiple cognitive domains, there are practical limits to what can be achieved in an investigation that has been piggybacked on to a trial with its own demanding protocol.Expediency is necessary to retain the cooperation of the investigators and subjects in this important collaboration.Nevertheless, not all of C D Irvine and S H Irvine's criticisms of our outcome measures are justified.Their contentions that the paired associate learning test may not be a valid measure of intellectual function in late life and that it lacks internal consistency are not supported by the reference that they cite.In research in older populations the validity ofthe test is established as an indicator of decline on the abbreviated mental test score,' as a correlate of cognitive and functional decline as measured by the psychogeriatric assessment
Left Atrial Ablation Versus Biatrial Ablation for Persistent and Permanent Atrial Fibrillation
Authors: Leonardo Calò, Filippo Lamberti, Maria Luisa Loricchio, Ermenegildo De Ruvo, Furio Colivicchi, Leopoldo Bianconi, Claudio Pandozi, Massimo Santini
Journal: Journal of the American College of Cardiology (2006)
Abstract 12747: Protein Profiling for Survival Outcome Prediction in Out-of-Hospital Cardiac Arrest Patients
Authors: Chien-Hua Huang, Min-Shan Tsai, Wei-Tien Chang, Hsin-Yun Hsu, Wen-Jone Chen
Journal: Circulation (2014)

Introduction: Outcome prediction is still a challenge for out-of-hospital cardiac arrest (OHCA) patients in early post-cardiac arrest period. Changes of protein expression after cardiac arrest and resuscitation could be biomarkers for outcomes prediction. Single biomarker can not reach adequate power to predict outcome due to the complexity of pathophysiological cascades in post-cardiac arrest period. Protein profiling can measure multiple biomarkers at a time point and can provide better information for outcome prediction. Hypothesis: Identify the association of survival to discharge outcome and biomarkers changes by protein profiling in cardiac arrest patients Methods: Total 99 adult non-traumatic OHCA patients with sustained ROSC were enrolled for the study. There were 45 patients survival to hospital discharge. Blood were sampled at 24 hours after cardiac arrest. Protein profiling for 21 different biomarkers, which included brain, heart, inflammatory reactions, oxidative stress and coagulation markers, was measured by suspension microarray assay. Clustering analyses were carried out using Multi-Experiment Viewer (MeV v4.8.1). Results: Heat maps were generated to visualize the Log2 values relative to median values of overall patient sample pool. Based on the performed statistical analysis to narrow down the biomarker panel, we investigated samples respectively by employing only the significant parameters for the Hierarchical Clustering (HCL) analysis. Nine candidate biomarkers (IL-6, IL-8, IL-10, MCP-1, MDA-LDL, Cystatin C, PAI-1, NT-Pro-BNP and S100B) identified respectively from samples pools were applied. The discrimination based on the selected parameters was 76.3% to be accurately clustered in HCL analysis. When adding these biomarkers into clinical variables (age, sex, Apache II, hypothermia, shockable rhythm, CPR duration), receiver-operating characteristic curve analysis showed high prediction power for survival to discharge (area under curve = 0.9378, p&lt;0.01) Conclusion: Protein profiling with suspension microarray can demonstrate the pattern of biomarkers in various pathophysiological changes after cardiac arrest. It has the potential to help predicting the outcome in OHCA patients.
Platelet MAO activity in anorexia nervosa patients with and without a major depressive disorder
Authors: J Biederman, T M Rivinus, D B Herzog, R A Ferber, G P Harper, P J Orsulak, J S Harmatz, J J Schildkraut
Journal: American Journal of Psychiatry (1984)

Platelet MAO activity was determined in 33 anorexia nervosa patients. A subgroup of 15 patients who met Research Diagnostic Criteria for a concomitant major depressive disorder were found to have, both initially and after 5 weeks of treatment, significantly lower mean platelet monoamine oxidase (MAO) activity than 28 matched normal control subjects. In contrast, mean platelet MAO activity in the patients who did not meet criteria for major depressive disorder was similar to values in control subjects. The authors found that significantly more depressed patients had low MAO activity compared with nondepressed patients and controls. Platelet MAO activity may be useful in discriminating among subtypes of anorexia nervosa patients.
G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis
Authors: Ahmad Antar, Zaher Otrock, Mohamed Kharfan-Dabaja, Hussein Abou Ghaddara, Nabila Kreidieh, Rami Mahfouz, Ali Bazarbachi
Journal: Blood (2014)
Abstract 11001: Cyclophilin a Mediates Pulmonary Vascular Remodeling by Rho-Kinase Activation in Patients With Pulmonary Hypertension
Authors: Kimio Satoh, Yoshihiro Fukumoto, Koichiro Sugimura, Shunsuke Tatebe, Yutaka Miura, Saori Miyamichi, Kazufumi Nakamura, Patrizia Nigro, Bradford C Berk, Hiroaki Shimokawa
Journal: Circulation (2010)

Background:  Pulmonary arterial hypertension (PAH) is associated with hypoxic exposure, enhanced reactive oxygen species (ROS) and proliferation of vascular smooth muscle cells (VSMC). We have recently demonstrated that ROS stimulate secretion of VSMC-derived cyclophilin A (CyPA) that promotes proliferation and migration of VSMC in vivo and in vitro. In addition, we reported that Rho-kinase is activated in patients with PAH. However, the role of CyPA in the pathogenesis of PAH in humans remains to be examined. In this study, we tested the hypothesis that CyPA contributes to Rho-kinase activation and pulmonary vascular remodeling in PAH patients.   Methods and Results:  We used lung tissue and pulmonary VSMC from 8 PAH patients who underwent lung transplantation and 6 controls (normal tissue from lung cancer patients). Immunostaining of the lung revealed that CyPA expression in pulmonary microvasculature (co-localized with αSMA +  cells) was greater in the PAH patients compared with the controls. The numbers of CD45 + , CD68 +  and CD3 +  cells in the lung were all significantly increased in the PAH patients compared with the controls (all P +  cells significantly correlated with CyPA expression, suggesting that CyPA is involved in VSMC proliferation. In response to hypoxic exposure (1%; O 2 , 24 hours), CyPA secretion as well as Rho-kinase activity were significantly increased as compared with normoxic condition (21%; O 2 , 24 hours) in VSMC and the extent of the hypoxia-induced CyPA secretion was markedly enhanced in PAH VSMC compared with control VSMC (P   Conclusions:  These results provide the direct evidence that the CyPA/Rho-kinase pathway plays an important role in the pathogenesis of PAH in humans.