tbuckley/cabot-search huggingface dataset:
Plasminogen activator inhibitor-1 and prognosis in primary breast cancer.
Authors: J A Foekens, M Schmitt, W L van Putten, H A Peters, M D Kramer, F Jänicke, J G Klijn
Journal: Journal of Clinical Oncology (1994)

PURPOSE Evaluation of the relationship between plasminogen activator inhibitor-1 (PAI-1) and the metastatic potential of primary breast cancer, and to compare the prognostic impact of PAI-1 in multivariate analysis with those of conventional prognostic factors, including steroid-hormone receptors, and those of urokinase plasminogen activator (uPA), pS2-protein (PS2), and cathepsin D. PATIENTS AND METHODS Cell biologic prognostic factors were analyzed in 657 cytosols routinely prepared from frozen-tissue biopsies that were submitted to our laboratory for the assessment of steroid-hormone receptor status. The median duration of follow-up in patients still alive at the time of analysis was 48 months. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assay, PS2, and cathepsin D by radiometric immunoassay, and uPA and PAI-1 by enzyme-linked immunosorbent assay (ELISA). RESULTS PAI-1 levels were found to be strongly positively correlated with the rates of relapse (P &lt; .0001) and death (P &lt; .001). Relating the levels of PAI-1 with those of other cytosolic prognostic factors, we found a positive association with the metastasis-related proteases uPA (P &lt; .0001) and cathepsin D (P &lt; .0001). On the other hand, PAI-1 levels were found to be negatively correlated with ER (P &lt; .005) and PgR (P &lt; .001), and the estrogen-regulated pS2-protein (P &lt; .001), which are proteins associated with a favorable prognosis. In multivariate regression analysis for 5-year relapse-free survival, and using an optimized cutoff point for discrimination between PAI-1-positive and -negative, independent predictors of the rate of relapse were found to be PAI-1 (P &lt; .0001) and uPA (P = .01) of the cytosolic parameters, and tumor size, lymph node status, and premenopausal age of the clinical parameters. In multivariate analysis in patients with node-negative disease, only PAI-1 (P &lt; .001) and tumor size (P = .03) were positively and premenopausal age negatively (P &lt; .001) associated with the rate of relapse. In patients with node-positive disease, PAI-1 (P &lt; .001), uPA (P = .02), tumor size (P &lt; .001), and the number of positive lymph nodes (P &lt; .001) were all positively associated with the rate of relapse. CONCLUSION We conclude that the PAI-1 level measured in routinely prepared cytosols is an important parameter to predict the metastatic potential in both node-negative and node-positive human primary breast cancer.
Selective-Serotonin-Reuptake-Inhibitors (SSRIs) In Combination With Myeloma Directed Therapy Accelerates Sentinel M-Protein Normalization In De-Novo Multiple Myeloma
Authors: Mathew Zheng, Sarvari Venkata Yellapragada, Martha Mims, Ruben Hernandez Perez, Gustavo A. Rivero
Journal: Blood (2013)
Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic
Authors: Kin Man Au, Andrew Satterlee, Yuanzeng Min, Xi Tian, Young Seok Kim, Joseph M. Caster, Longzhen Zhang, Tian Zhang, Leaf Huang, Andrew Z. Wang
Journal: Biomaterials (2015)
Is Vagal Denervation a Good Alternative or Just Adjunctive to Pulmonary Vein Isolation in Catheter Ablation of Atrial Fibrillation?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jen-Yuan Kuo, Shih-Ann Chen
Journal: Journal of the American College of Cardiology (2007)
Fcγ-receptor 3B ( FCGR3B ) copy number variations in patients with eosinophilic granulomatosis with polyangiitis
Authors: Davide Martorana, Francesco Bonatti, Federico Alberici, Andrea Gioffredi, Michele Reina, Maria L. Urban, Federica Maritati, Alessia Adorni, Antonella Radice, Silvia Pizzolato, Gina Gregorini, Guido Jeannin, Giuseppe Guida, Monica Boita, Alberto Pesci, Gabriella Moroni, Tauro M. Neri, Renato A. Sinico, Augusto Vaglio
Journal: Journal of Allergy and Clinical Immunology (2015)
Inflammatory status affects the antitumor activity of poly-epitope-peptide vaccination against the thymidylate synthase in metastatic colo-rectal cancer patients enrolled in TSPP/VAC-1 Phase Ib trial
Authors: Pierpaolo Correale, Valerio Nardone, Cirino Botta, Elodia Martino, Pierpaolo Pastina, Cristina Ulivieri, Maria Rossetti, Antonella Fioravanti, Claudia Gandolfo, Francesco Carbone, Tatiana Baldari, Pierosandro Tagliaferri, Luigi Pirtoli, Maria Cusi
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Thymidylate synthase (TS) is a tumor-associated-enzyme crucial for DNA replication and inhibited by 5′-fluorouracil. TSPP is a previously characterized anticancer poly-epitope peptide vaccine to TS ( Correale P, JNCI 2005 97:1437 ). TSPP/VAC-1 is a three-arm dose-finding Phase-
Abstract 15288: Conductive Polymer Hydrogel for Enhancement of Electrical Propagation in Border Zone Myocardium after Myocardial Infarction
Authors: Anton Mihic, Yasuo Miyagi, Jun Wu, Goran Vlacic, Martin Lam, Zui Cui, Shu-hong Li, Lu Sun, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2014)

Introduction: After myocardial infarction (MI), cardiomyocyte death results in a non-contractile fibrotic scar and altered electrical properties, including delayed impulse propagation across the scar region which may contribute to ventricular dysfunction. Hydrogels such as chitosan have been used clinically to stabilize the LV free wall and prevent dilation. We chemically modified chitosan with the charge-carrying conductive polymer polypyrrole (PPy), yielding a biomaterial with more than 100X the conductivity of chitosan alone. Chitosan-PPy is capable of carrying electrical impulses and may enhance synchronous contraction. Methods: Biomaterials were synthesized under sterile conditions and were thoroughly characterized in vitro . Myocardial infarction was created by coronary artery ligation in Sprague-Dawley rats (n = 36), and 1 week later chitosan, chitosan-PPy or saline were injected into the border zone regions. Animals were followed for 8 or 16 weeks (n = 6/treatment/time-point) and cardiac conduction and function were assessed with ECG, echocardiography, impedance catheter analysis and finally Langendorff-perfused epicardial optical mapping. Results: Eight weeks post-injection, QRS duration was increased in saline and chitosan treated hearts, but was maintained in chitosan-PPy hearts until 16 weeks ( p &lt; 0.01), suggesting less maladaptive ventricular remodeling associated with slowing of depolarizing conduction in the chitosan-PPy group. Echocardiography revealed that fractional shortening was enhanced in chitosan-PPy treated hearts at both 8 and 16 weeks ( p &lt; 0.01). At 16 weeks, chitosan-PPy hearts had increased stroke work capacity, and better maintained (lower) end systolic volume ( p &lt; 0.05). Optical mapping demonstrated that chitosan-PPy-treated hearts had faster transverse conduction velocities measured along the border zone epicardial surface ( p &lt; 0.01). Conclusions: We synthesized and characterized a novel conductive polymer hydrogel that may be used therapeutically to enhance favorable cardiac recovery at the LV border zone following an MI. Chitosan-PPy enhanced heart function by augmenting synchronized contraction.
Roles of palmitoylation and the KIKK membrane-targeting motif in leukemogenesis by oncogenic KRAS4A
Authors: Huanbin Zhao, Ping Liu, Ruihong Zhang, Min Wu, Donghe Li, Xuemei Zhao, Chun Zhang, Bo Jiao, Bing Chen, Zhu Chen, Ruibao Ren
Journal: Journal of Hematology & Oncology (2015)

We have previously shown that palmitoylation is essential for NRAS leukemogenesis, suggesting that targeting RAS palmitoylation may be an effective therapy for NRAS-related cancers. For KRAS-driven cancer, although much research has been focused on the KRAS4B splice variant, which does not undergo palmitoylation, KRAS4A has recently been shown to play an essential role in the development of carcinogen-induced lung cancer in mice and to be widely expressed in human cancers. However, the role of palmitoylation in KRAS4A tumorigenesis is not clear. The expression of KRAS4A in KRAS-mutated leukemia cell lines and acute myeloid leukemia (AML) cells were checked using western blotting and reverse transcriptions-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively. The leukemogenic potentials of oncogenic KRAS4A and its palmitoylation-defective mutants were examined by a mouse bone marrow transduction and transplantation model and the in vitro transformation assays. The activation of the RAS downstream signaling pathways and the membrane localizations of the KRAS4A and its mutants were analyzed via western blot analysis and confocal microscopy, respectively. We show here that KRAS4A is expressed in human leukemia cell lines and in AML cells harboring KRAS mutations and that mutation at the palmitoylation site of oncogenic KRAS4A significantly abrogates its leukemogenic potential. However, unlike NRAS, palmitoylation-defective KRAS4A still induces leukemia in mice, albeit with a much longer latency. Using NRAS/KRAS4A chimeric constructs, we found that the KIKK motif of KRAS4A contributes to the transforming activity of KRAS4A. Mutations at both palmitoylation site and the KIKK motif abolish the ability of oncogenic KRAS4A to induce leukemia in mice. Our studies suggest that therapies targeting RAS palmitoylation may also be effective in treating KRAS4A associated malignancies and that interfering the KIKK membrane-targeting motif would enhance the therapeutic effectiveness.
Lung Cancer Presenting With Solitary Bone Metastases
Authors: Kristen N. Ganjoo, Joyce A. Loyal, Harvey M. Cramer, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.9.2995 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561377 Lung Cancer Presenting With Solitary Bone Metastases Kristen N. GanjooxKristen N. GanjooSearch for articles by this author , Joyce A. LoyalxJoyce A. LoyalSearch for articles by this author , Harvey M. CramerxHarvey M. CramerSearch for articles by this author , Patrick J. LoehrerxPatrick J. LoehrerSearch for articles by this author Show More Department of Medicine, Division of Hematology/Oncology, Indiana University Medical Center, The Walther Cancer Institute, and Department of Pathology, Division of Cytopathology, Indiana University Medical Center, Indianapolis, IN https://doi.org/10.1200/JCO.1999.17.9.2995 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Resting Hyperperfusion of the Hippocampus, Midbrain, and Basal Ganglia in People at High Risk for Psychosis
Authors: Paul Allen, Christopher A. Chaddock, Alice Egerton, Oliver D. Howes, Ilaria Bonoldi, Fernando Zelaya, Sagnik Bhattacharyya, Robin Murray, Philip McGuire
Journal: American Journal of Psychiatry (2015)

Objective: Animal models suggest that the development of psychosis involves hyperactivity in the hippocampus that drives increased activity in the midbrain and basal ganglia. The authors examined this hypothesis by measuring resting perfusion in the hippocampus, basal ganglia, and midbrain in people at high risk of psychosis. Method: Pseudo-continuous arterial spin labeling imaging was used to measure resting regional cerebral blood flow (rCBF) in 52 individuals at ultra-high risk for psychosis and in 27 healthy volunteers. The severity of psychotic symptoms was assessed using the Comprehensive Assessment of At-Risk Mental States. The ultra-high-risk subjects were reassessed after a mean of 17 months, using the same measures as at baseline. Results: At baseline, relative to healthy volunteers, ultra-high-risk subjects showed elevated rCBF in the hippocampus, basal ganglia, and midbrain. In the ultra-high-risk sample overall, at follow-up, symptomatic improvement and reduced rCBF in the hippocampus and ventral striatum were observed. Subjects whose symptoms had resolved such that they no longer met ultra-high-risk criteria showed a longitudinal reduction in left hippocampal rCBF that was not evident in subjects who remained in a high-risk state or had become psychotic. Conclusions: A high risk for psychosis was associated with increased resting activity in the hippocampus, midbrain, and basal ganglia. Subsequent resolution of the high-risk state was linked to a normalization of activity in these regions. These findings are consistent with animal models that propose that psychotic symptoms may be generated when hippocampal hyperactivity drives hyperactivity in regions involved in subcortical dopamine signaling.
Multicenter Phase Ib/II Trial of the Radiation Enhancer Motexafin Gadolinium in Patients With Brain Metastases
Authors: Patrice Carde, Robert Timmerman, Minesh P. Mehta, Christopher D. Koprowski, Judith Ford, Roy B. Tishler, Dale Miles, Richard A. Miller, Markus F. Renschler
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Motexafin gadolinium is a magnetic resonance imaging (MRI)–detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase Ib/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. PATIENTS AND METHODS: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase Ib, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. RESULTS: In phase Ib, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium’s tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. CONCLUSION: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.
Magnetic resonance imaging is not a sensitive test for Creutzfeldt-Jakob disease
Authors: M. Zeidler, R G Will, J W Ironside, R Sellar, J Wardlaw
Journal: BMJ (1996)

develop the disease when old: crudely, we now have six annual cohorts of 1 year olds but only one annual cohort of 6 year olds.Assuming that the diagnoses for cows born after the ban were made between January 1990 and October 1995, I have calculated the number of annual cohorts of calves implicit in each age group of such diagnoses (table 1).The final column of the table then lists by age the number of diagnoses per annual cohort.These figures are thus equivalent to the column for the single year 1989.The age structure of diagnoses can indeed be seen to have changed little.What is surprising, however, is that the incidence of the disease increased substantially after the ban.Among 5 year olds, for example, 1874 of those born in 1984 were affected; this figure increased to roughly 4353 of those born in 1989.Perhaps the Ministry of Agriculture, Fisheries and Food could supply the exact figures.
Mutation in MMP2 gene may result in scleroderma-like skin thickening
Authors: B Bader-Meunier, L Bonafé, S Fraitag, S Breton, C Bodemer, G Baujat
Journal: Annals of the Rheumatic Diseases (2015)

Mutation in MMP2 gene may result in scleroderma-like skin thickeningWe read with interest the paper by Banka et al 1 who identify microduplications of chromosome 8q22 as the cause of Leri's pleonostosis, a disease belonging to the 'transforming growth factor beta (TGF-beta)-pathies' group of musculoskeletal disorders.We have been involved in the identification of rare monogenic systemic lupus erythematosus (SLE), especially inherited interferonopathies, 2 3 and we agree with the authors that the common phenotype of autoimmune diseases, such as SLE and systemic sclerosis (SSc), could be explained by involvement of different disease-associated genes in related physiological pathways.Herein we aim to report for the first time that mutation in matrix metalloproteinase-2 (MMP-2) may result in scleroderma-like skin thickening.A 12-year-old girl was referred because of distal osteoporosis revealed by several pathological appendicular fractures since the age of 8 years.There was no family history.Physical evaluation revealed mildly coarse face, hypertrophic scars and keloids, gum hypertrophy, nodules on the soles, painless contractures of small joints and diffuse skin thickening.Figure 1 Wrist MRI: small erosive changes of the carpal and proximal metacarpals and enhancement of the synovial were detected.
Use of the UCLA-integrated staging system (UISS) to predict survival after sunitinib treatment for patients with metastatic renal cell carcinoma.
Authors: F. Pouliot, C. Anterasian, T. Klatte, D. Finley, B. Shuch, F. F. Kabbinavar, N. Zomorodian, A. S. Belldegrun, A. J. Pantuck
Journal: Journal of Clinical Oncology (2010)

4593 Background: During the immunotherapy (IT) era of treating metastatic renal cell carcinoma (mRCC), multivariate prognostic systems such as the UISS were shown to better predict prognosis than TNM staging alone. With the development of targeted receptor tyrosine kinase inhibitors (TKIs), IT is now only an option available. Validation of IT-era integrated nomograms in TKI-treated patient cohorts is of utmost importance to compare efficacy of the available treatments and to better select treatments for mRCC patients. In this study, we have analyzed the ability of the UISS to predict response and survival to sunitinib (SU). Methods: Data from 69 patients who received SU for mRCC following nephrectomy were retrospectively reviewed. Results: The basic characteristics of the cohort of patients were as follow: 87 % were clear cell carcinoma histology; ECOG at time of nephrectomy vs at time of SU was 0 (75 vs 84 %), 1 (23 vs 15 %) and 2 (1 vs 1 %) ; 65 % of tumors were Fuhrman grade 3/4; UISS 1-, 2- and 3- groups at time of nephrectomy (UISS-Nx) vs at SU (UISS-SU) were 27 vs 30 , 63 vs 58 and 11 vs 12, respectively; median OS for the entire cohort following SU was 19.3 months. Sixty four percent of patients had progressive or stable disease as best response, while 36% had partial response. The most significant clinical predictive factors for response to SU were UISS-Nx (p=0.06) and UISS-SU (p=0.05), while statistically significant prognostic factors for OS were clinical response (p=0.007), Fuhrman grade (p=0.006), UISS-Nx (p=0.0001) and UISS-SU (p=0.004). Concordance analysis revealed that UISS-Nx (69 %) and UISS-SU (67 %) were the most important factors predicting OS. Conclusions: We have validated the UISS as an accurate clinical prognostic system to estimate OS and to predict treatment response for SU when used as treatment for mRCC. The UISS can be applied both at the time of nephrectomy and at the time of initiation of systemic therapy. By better predicting OS than clinical parameters alone, the UISS will help oncologists to better stratify mRCC patients into risks groups, and will allow relevant survival comparison between historical IT and new treatment regimens. No significant financial relationships to disclose.
Water soluble PEG-conjugate of xanthine oxidase inhibitor, PEG–AHPP micelles, as a novel therapeutic for ROS related inflammatory bowel diseases
Authors: Jun Fang, Hongzhuan Yin, Long Liao, Haibo Qin, Fumiko Ueda, Kyoko Uemura, Kanami Eguchi, Gahininath Y. Bharate, Hiroshi Maeda
Journal: Journal of Controlled Release (2015)
Chemotherapy plus cyclosporine A for the treatment of intraocular retinoblastoma: The University of Miami Miller School of Medicine experience
Authors: C. E. Fernandes, A. C. Schefler, T. G. Murray, J. A. Davis, O. A. Alvarez, A. Podda, J. C. Barredo, E. White, N. Lewis, S. R. Toledano
Journal: Journal of Clinical Oncology (2007)

20005 Background: In the past decade chemotherapy and focal control became the standard of care in retinoblastoma. The ideal chemotherapy regimen has not yet been determined. We analyzed the results of treatment at the University of Miami Miller School of Medicine using the regimen carboplatin (20 mg/kg, day 1), vincristine (0.05 mg. /kg, day 1), etoposide (5 mg / kg, days 1 and 2) with or without cyclosporine A (10 mg. /kg over 2 hours followed by 45 mg/kg over 31 hours) every 3–4 weeks. We attempted to maintain peak CSA levels between 2,400 and 6,000 and steady state levels between 2,400 and 4,200 ng/ml. When CSA was given, vincristine was started at 0.0125 mg /kg. The dose was escalated by 25% with each cycle of therapy, as tolerated. Methods: A retrospective analysis was performed in 41 patients diagnosed with bilateral retinoblastoma from Dec 1996 to Jan 2006. Only eyes with intraocular disease (76 eyes) were included in this analysis. Before each cycle of chemotherapy ophthalmologic examination under anesthesia was performed and active tumor and seeding were treated with local ablation using laser therapy. Eyes in which enucleation was planned at diagnosis were excluded from this analysis. Results: Most patients received 9 cycles of chemotherapy. Sixty percent (46/76) of the eyes were treated with chemotherapy and CSA. The eye salvage rate for eyes classified by the International Classification of Retinoblastoma (ICRB) as groups A, B, C and D was 100%. The eye salvage rate for the 21 eyes classified as ICRB group E was 29%. No difference in salvage rate was observed in eyes treated with or without CSA. One patient died from disease progression. Only one patient required radiation therapy to both eyes. To date there have been no reports of development of secondary malignancies. Conclusion: The addition of CSA to the treatment of the eyes classified as ICRB groups A, B, C and D made no difference in the eye salvage rate. Also, we were not able to demonstrate any benefit from the addition of CSA in patients with stage E eyes- although our sample size was quite small. Aggressive focal control and chemotherapy beginning at diagnosis may be the reason for the excellent EFS in group A, B, C and D eyes. No significant financial relationships to disclose.
IOP measurements after PRK11The following two letters address an article that appeared in the December 1998 issue of the Journal:Abbasoglu OE, Bowman RW, Cavanagh HD, McCulley JP. Reliability of intraocular pressure measurements after myopic excimer photorefractive keratectomy.(Ophthalmology 1998;105:2193–6)
Authors: Lance C Lemon
Journal: Ophthalmology (1999)