tbuckley/cabot-search huggingface dataset:
Expression of the WAVE (WASP Verprolin-homologous) molecules in human breast cancer
Authors: H. Fernando, A. Chhabra, S. Davies, G. Watkins, H. Kynaston, R. E. Mansel, W. G. Jiang
Journal: Journal of Clinical Oncology (2007)

21061 Background: WAVEs (WASP Verprolin-homologous) belongs to the CCN family which comprises of nine members, the cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and nephroblastoma over-expressed (Nov/CCN3), Wnt-induced secreted proteins(WISPs)1, 2 and 3 (CCN4–6) as well as the WAVE-1,2 and 3 (also known as CCN7–9 respectively). Some members of the CCN family, such as Cyr61 and CTGF are known to stimulate mitosis, adhesion, apoptosis, extracellular matrix production, cell migration and growth arrest in cancer cells including breast cancer cells. However, there is no knowledge of the expression pattern and the function of WAVEs in human breast cancer. Here, we report the expression of WAVE-1,-2 and -3 transcripts and proteins in relation to clinical and pathological characteristics in human breast cancer. Methods: The expression of the three WAVE molecules at the mRNA and protein levels in a cohort of 122 human breast cancers and 32 normal breast tissues were analysed and correlated with the patients’ clinical outcome. The respective transcripts were quantitative determined using real time RT-PCR and distribution of the proteins were investigated by immunohistochemical methods. Results: All three WAVE proteins were detected in mammary epithelial cells and are of cytoplasmic nature. Breast cancer cells from the tissues also displayed positive staining of the WAVE proteins, with WAVE-2 staining appears weaker compared with normal epithelial cells. WAVE-1 transcripts were expressed in significantly high levels (p=0.03) in high grade breast cancers. Low levels of WAVE-2 were associated with higher TNM staging (p=0.038 in TNM3 and p=0.017 in TNM4) and were also found in patients with poor prognosis. Interesting, a marginal reduction of WAVE-3 transcripts was seen in patients who developed systemic metastasis. No other significant associations were found between the WAVE1 and WAVE3 transcripts and the breast cancer cells. Conclusions: WAVEs are widely expressed in human mammary tissues and have a differential expression in human breast cancer with WAVE2 appearing to be associated with the aggressiveness of breast tumors. No significant financial relationships to disclose.
Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
Authors: Neil H. Segal, Theodore F. Logan, F. Stephen Hodi, David McDermott, Ignacio Melero, Omid Hamid, Henrik Schmidt, Caroline Robert, Vanna Chiarion-Sileni, Paolo A. Ascierto, Michele Maio, Walter J. Urba, Tara C. Gangadhar, Satyendra Suryawanshi, Jaclyn Neely, Maria Jure-Kunkel, Suba Krishnan, Holbrook Kohrt, Mario Sznol, Ronald Levy
Journal: Clinical Cancer Research (2016)

Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma.Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included treatment-related and serious adverse events (AEs), as well as treatment-related AEs leading to discontinuation and death, with a focus on liver function test abnormalities and hepatic AEs.Results: Urelumab doses between 1 and 15 mg/kg given every 3 weeks resulted in a higher frequency of treatment-related AEs than 0.1 or 0.3 mg/kg every 3 weeks. Dose was the single most important factor contributing to transaminitis development, which was more frequent and severe at doses ≥1 mg/kg. At the MTD of 0.1 mg/kg every 3 weeks, urelumab was relatively well tolerated, with fatigue (16%) and nausea (13%) being the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines.Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg/kg. However, urelumab 0.1 mg/kg every 3 weeks was demonstrated to be safe, with pharmacodynamic activity supporting continued clinical evaluation of this dose as monotherapy and in combination with other immuno-oncology agents. Clin Cancer Res; 23(8); 1929-36. ©2016 AACR.
The BMJ Awards: celebrating excellence
Authors: Fiona Godlee
Journal: BMJ (2016)

This week both houses of parliament have put their minds to the NHS funding crisis (p 127). A House of Lords committee hearing on the sustainability of NHS funding was told by Chris Hopson, chief executive of NHS Providers, that the health service had reached a “tipping point” where it was being asked to deliver services “that it simply cannot carry on delivering for the funding available.”

Also in this issue Andy Cowper (p 130) reports that the pressure on the health service in England continues to build and its performance to suffer, made more acute by …
Donor T-Cell Chimerism Does Not Predict Relapse and Response to Donor Lymphocyte Infusion for a Patient of Secondary Acute Myeloid Leukemia after Reduced-Intensity Allogeneic Hematopoitic Stem Cell Transplantation.
Authors: Xiaowen Tang, Qiurong Zhang, De Pei Wu, Yufeng Feng, Aining Sun
Journal: Blood (2006)
Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition
Authors: Barbara Kutryb-Zajac, Lukasz Mateuszuk, Paulina Zukowska, Agnieszka Jasztal, Magdalena A. Zabielska, Marta Toczek, Patrycja Jablonska, Agnieszka Zakrzewska, Barbara Sitek, Jan Rogowski, Romuald Lango, Ewa M. Slominska, Stefan Chlopicki, Ryszard T. Smolenski
Journal: Cardiovascular Research (2016)

Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis.Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular inflammation and improved endothelial function.This study highlights the importance of extracellular nucleotides and adenosine metabolism in the atherosclerotic vessel in both experimental and clinical setting. The increased eADA activity marks an early stage of atherosclerosis, contributes to its progression and could represent a novel target for therapy.
Defibrillators made by St Jude Medical are prone to battery failure, FDA warns
Authors: Michael McCarthy
Journal: BMJ (2016)

Two defibrillators manufactured by St Jude Medical are prone to failure because of faulty batteries, the US Food and Drug Administration (FDA) warned in a safety communication issued on 11 October.1

The warning applies to implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRT-D) manufactured before May 2015, which are used to provide pacing for patients with bradycardia, defibrillation for those with dangerous tachycardias, and synchronization to improve cardiac function in patients with heart failure.

The devices should issue an alert, known as an elective replacement indicator (ERI) alert, when their batteries are …
GW26-e1388 Transplantation of EPCs Overexpressing S1PR3 Promotes Vascular Repair in the Early Phase After Vascular Injury
Authors: Hang Wang, Keyin Cai, Li Wang, Kehong Zhao, Ying Tu, Xiao Wang, Jiahuan Li, Hao Huang
Journal: Journal of the American College of Cardiology (2015)
Are Red Cell Indices a Reliable Screening Tool in Pre-Natal Screening for the Avoidance of E-Beta Thalassemia and Beta Thalassemia Major Births? Results of a Population Survey From Eastern India
Authors: Shyamali Dutta, Tuphan Dolai, Rajat Kumar, Maitreyee Bhattacharyya, Barnali Chakraborti, Sharmistha Sanyal, Swarupa Bhattacharjee, Basab Bagchi, Rajib De, Malay K Ghosh
Journal: Blood (2011)
Results of omacetaxine plus low-dose cytarabine (LD-araC) in older patients with acute myeloid leukemia (AML).
Authors: Tapan M. Kadia, Naval Guastad Daver, Farhad Ravandi, Elias Jabbour, Naveen Pemmaraju, Sherry Pierce, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2013)

7068 Background: Older patients with AML have poor tolerance to intensive chemotherapy and poor prognosis. Omacetaxine is active in AML and is part of standard combination chemotherapy in China under the name of homoharringtonine. Methods: The aim of the study was to evaluate the efficacy of low intensity therapy with omacetaxine and LD-ara C in newly diagnosed older patients (&gt;/= 60 years) with AML or myelodysplastic syndrome (MDS). Older patients with AML not fit or who refuse intensive chemotherapy were eligible. Normal organ functions and performance status &lt;/= 2 were required. Other eligibility criteria were standard. Induction therapy consisted of omacetaxine 1.25 mg/m2 subcutaneously twice daily for 3 days and ara-C 20 mg subcutaneously twice daily for 7 days. Maintenance therapy was with the same induction schedule, repeated every 4-6 weeks for up to 2 years. Dose adjustments for prolonged myelosupression or severe non-hematologic toxicities were made by reducing the number of days of omacetaxine (-1 day by level) and cytarabine (-1 to 2 days by level). Results: 30 patients have been treated, with a median age of 71 years (range 64-81); 60% were age 70 years or older. AML post MDS in 20%; chromosome 5 and 7 abnormalities were present in 23%. Overall, 9 patients achieved CR (30%), 5 had CRp (17%) and 1 had PR (3%), for an overall response rate of 50%. Induction mortality was noted in 4 (Day 5, 27, 27, and 70 from start of therapy; 13%); resistant disease in 8 (27%); too early in 4 (13%). With the median follow-up time of 10 months the median survival is 9.3 months and the estimated 1-year survival rate 42%. No serious drug related adverse effects were observed with the combination. Conclusions: Low-intensity therapy with omacetaxine + LD-ara C shows promising activity and is safe in older patients with AML not fit for intensive chemotherapy. Clinical trial information: NCT01272245.
GW26-e1335 siRNA Inhibits AT2 Receptor In decreasing NO Generation by Recombinant Human Angiotensin converting Enzyme 2 in Cardiac Microvascular Endothelial Cells
Authors: Yan Zhang, Congxia Wang, Chunyan Zhang, Weidong Ma, Yongqin Li
Journal: Journal of the American College of Cardiology (2015)
P0208 : Hemodynamic response to non-selective beta-blockers is not influenced by the presence of metabolic syndrome
Authors: S. Bota, P. Schwabl, M. Mandorfer, P. Salzl, R. Schwarzer, A. Ferlitsch, M. Trauner, M. Peck-Radosavljevic, T. Reiberger
Journal: Journal of Hepatology (2015)
Role of Brazilian native medicinal plants on VEGF and PDGF receptors expression by glioblastoma cell line GL-15
Authors: C. Mathias, I. Nascimento, G. Carvalho, R. Meyer, A. Queiroz, S. Freitas, S. Freire, E. Veloso, P. Barbosa, S. Costa, C. Azevedo
Journal: Journal of Clinical Oncology (2007)

12532 Background: Malignant gliomas are typically angiogenic and express greater amounts of angiogenic factors. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are prominent glioblastoma-associated multifunctional cytokines that stimulate migration, invasion and angiogenesis. Their receptor inhibiton is considered an important target for anitumoral therapy. Flavonoids obtained from Dimorphandra mollis and Croton betulaster, native medicinal plants from Bahia-Brazil, have been described as proliferation inhibitors of a human glioblastoma derived cell line and reduce VEGF production by GL-15. In this study, VEGF and PDGF receptors expression by GL-15 cultures treated with bevacizumab and flavonoids were evaluated. Methods: GL-15 cultures were treated or not with pendulitin and rutin flavonoids (100μM) and bevacizumab (1μg/mL). After 24 hours VEGF and PDGF receptors were analyzed by flow cytometry using monoclonal antibodies labeled with FITC. Results: Flow cytometry showed that the GL-15 cells expressed PDGFR alfa (10%), PDGFR beta (52%), VEGFR 1 (26%) and VEGFR 2 (95%). It was observed that the pendulitin and rutin flavonoids treated cells showed a reduction on PDGFR alfa expression (2 and 1,6 % respectively) but the other receptors expression was similar to the non-treated or DMSO treated controls. Conclusions: GL-15 human glioblastoma derived cell line expresses receptors to the angiogenic cytokines studied. VEGFR 2 expression was predominant and bevacizumab didn’t alter the receptors production. Flavonoids extracted from D. mollis and C. betulaster seem to have an inhibitory action on the PDGRF alfa expression but not on the others receptors. No significant financial relationships to disclose.
The Quest to Improve Quality
Authors: Elizabeth A. McGlynn, John L. Adams, Eve A. Kerr
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
GW26-e3875 Diabetes Blunt the Compensatory Enhancement of SUMOylation Intensity of Sarcoplasmic Reticulum Calcium-transporting ATPase After Myocardial Infarction
Authors: Jing Yao, Tian-Chang Li, Shao Xing-Hui, Zheng-Ming Xu, Meng-Yue Yu, Si-Yong Teng, Yong-Jian Wu
Journal: Journal of the American College of Cardiology (2015)
Long-term administration of oblimersen (OBL) plus chemotherapy: An analysis of safety in patients with solid tumors and hematologic cancers
Authors: N. A. Baron, E. Gilles, S. Novick, J. Ehlert, J. Wu
Journal: Journal of Clinical Oncology (2007)

14098 Background: Oblimersen (OBL; Genasense®) is designed to increase the efficacy of cancer therapy by reducing Bcl-2 protein. The agent has been studied in several randomized clinical trials, which prompted an evaluation of safety after extended administration in combination with various anticancer agents. Methods: We evaluated safety data from more than 900 patients (pts) with solid tumors or hematologic cancers who received OBL alone or in combination with chemotherapy in phase I-III studies. A total of 84 pts (65 with solid tumors, 19 multiple myeloma) who received OBL for = 6 months of on-cycle and between-cycle days were identified. We then compared the incidence of adverse events (AEs) in the Day (D) 1 to D180-period with the &gt; D180 day period. Pts with solid tumors received OBL (0.6 to 12 mg/kg/d) in combination with dacarbazine, docetaxel, or mitoxantrone; pts with myeloma received OBL (7 mg/kg/d) combined with high-dose dexamethasone. Results: Among pts with solid tumors, the mean (± SD) number of 21 to 28-day cycles initiated was 12.3 (± 3.7; range, 7–25); the mean number of OBL treatment days was 65.6 (± 24.0; range, 45–156). In pts with myeloma, the mean number of 21 to 28-day cycles initiated was 13.3 (± 3.3; range, 9–20); the mean number of OBL treatment days was 105.3 (± 23.2; range, 77–148). Across both data sets, the incidence of AEs was lower or comparable in most system-organ classes (SOCs) in the &gt; 180-day period compared with the D1 to D180-period. Events were consistent with those reported with short-term administration in multiple studies, and common AEs (including fatigue, fever, nausea, and vomiting) were similar in both periods. Conclusions: Oblimersen can be safely combined with multiple types of anticancer therapy. Prolonged treatment with these combinations for &gt; 180 days has not been associated with the emergence of AEs qualitatively different from those reported with treatment for shorter periods. No significant financial relationships to disclose.
Predictors for toxicity profiles of weekly docetaxel in non-small cell lung cancers
Authors: J. P. Chen, Y. Lo, C. J. Yu, C. Hsu, J. Y. Shih, A. Cheng, P. C. Yang, C. H. Yang
Journal: Journal of Clinical Oncology (2006)

17153 Background: Weekly docetaxel has been proved recently to be safer and equivalently effective compared with traditional tri-weekly docetaxel as second-line treatment for NSCLC. However, the risk factors for toxicity of weekly docetaxel in this group of patients are still unknown. Methods: We reviewed advanced NSCLC patients receiving 2 nd line or 3 rd line weekly docetaxel from 1999 to 2003 from cancer registry and pharmacy records in our hospital. Clinical characteristics, previous chemotherapy regimens, laboratory data, docetaxel administration schedules/dosage, and treatment efficacy were retrospectively collected. Logistic regression was performed to identify risk factors for adverse outcomes. Cox’s proportional hazards model was used to analyze cumulative-dose related adverse events. Results: A total 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel (36–40 mg/m 2 ) was 5.16% and median survival of all patients was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.23 % and significantly related to previous anthracycline use (odds ratio 4.582; P = 0.0144) and chronic hepatitis B or C virus (HBV/HCV) infection(odds ratio 3.928; P=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio 7.232; P &lt; 0.001), lower baseline white count(odds ratio 5.57; P &lt; 0.05), and chronic HBV/HCV infection(odds ratio 3.25; P &lt; 0.05). The incidence of fluid retention was 41.29% and the median cumulative dose of docetaxel at onset was 327 mg/m 2 . Abnormal liver function significantly increased the risk for fluid retention(odds ratio 2.368; P &lt; 0.05); steroid premedication (odds ratio 0.184; P &lt; 0.01), higher albumin(odds ratio 0.237; P &lt; 0.01), and previous surgical resection(odds ratio 0.341; P &lt; 0.05) decreased the risk. Conclusions: Salvage weekly docetaxel for NSCLC patients in Taiwan remains toxic. Part of the reasons for the significant toxicities is that chronic HBV/HCV infection, which occurs in around 20% of general populations in Taiwan, represents a significant risk factor for neutropenia, fluid retention, and treatment withdrawal. The role of prophylactic anti-viral agents in these patients should be explored in the future. [Table: see text]
GW26-e3870 Gender-Related Differences in the Relationship between Plasma Homocysteine levels and lifestyle factors in rural Chinese population
Authors: Shuang Chen, Xiaofan Guo, Xingang Zhang, Shasha Yu, Hongmei Yang, Mohan Jiang, Guozhe Sun, Zhao Li, Liqiang Zheng, Yingxian Sun
Journal: Journal of the American College of Cardiology (2015)
The Role of PI3K Signaling in Cell Trafficking of Multiple Myeloma
Authors: Feda Azab, Abdel Kareem Azab, Patricia Maiso, Phong Quang, Hai T Ngo, Antonio Sacco, Yang Liu, Yong Zhang, Michaela Reagan, Aldo M Roccaro, Irene M. Ghobrial
Journal: Blood (2011)
Yttrium-90 (90Y) ibritumomab tiuxetan for treatment of relapsed or refractory non-hodgkin’s lymphoma: The Western Pennsylvania Cancer Institute experience
Authors: S. Jasthy, N. Sudan, B. Haq, J. Lister
Journal: Journal of Clinical Oncology (2006)

12511 Background: Yttrium-90 ( 90 Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an effective agent for treatment of CD20+ B-cell lymphoma (NHL).It is approved for treatment of relapsed or refractory, follicular or transformed B cell lymphoma. An overall response rate ranging from 74% to 82% has been reported. Median response duration of 11.5 to 28.1 months has been reported. Methods: We identified, retrospectively, 37 patients treated at our institution with relapsed or refractory NHL who were treated with 90 Y ibritumomab tiuxetan at a dose of 0.3mCi/kg or 0.4mCi/kg. Response rate and survival were assessed. Median age was 60 years (range 28–82 years) of which 65% were male. Follicular lymphoma was present in 57% (n = 21) and diffuse large B-cell lymphoma in 22% (n = 8) of patients. Advanced disease (stage III or IV) was present in 84% (n = 31) of patients. All of the patients had received at least one prior regimen and 68% (n = 25) had received ≥ 3 regimens before 90Y ibritumomab tiuxetan. Results: Overall response rate was 65% (24/37); CR 43% (16/37); PR 19% (7/37); SD 3% (1/37). Duration of response was 13.3 months (range 4 to 48 months) with response duration greater than 12 months in 35% (n = 13) of the patients. Of responders, 67% (16/23) had failed to respond to prior immediate therapy. The only toxic event was pancytopenia, which predictably occurred after treatment. No patients died of toxicity and all toxicity was reversible. Conclusions: 90 Y ibritumomab tiuxetan was well tolerated and effective for our patients.We document durable response in our patients with relapsed or refractory NHL and with advanced stage disease. Further study of ibritumomab tiuxetan using different doses and in combination with chemotherapy is warranted. No significant financial relationships to disclose.