tbuckley/cabot-search huggingface dataset:
Rituximab administration as part of initial therapy may be associated with a poorer outcome in young patients subsequently treated with stem cell transplantation for relapsed chemosensitive large B-cell lymphoma
Authors: S. M. Ansell, K. M. Ristow, D. J. Inwards, I. N. M. Micallef, L. F. Porrata, T. M. Habermann, P. B. Johnston, M. R. Litzow
Journal: Journal of Clinical Oncology (2005)

6665 Background: Treatment with rituximab in combination with CHOP chemotherapy (R-CHOP) has become standard as initial therapy for diffuse large B-cell lymphoma (DLBCL). Although concerns regarding increased resistance of DLBCL to further therapy after failing R-CHOP have been raised, recent data have suggested that the administration of rituximab prior to autologous stem cell transplantation (ASCT) does not affect the outcome of these patients. Methods: To corroborate these findings in a more uniformly treated patient population, we retrospectively analyzed 130 patients treated at a single institution between 1998 and 2003. Only patients with DLBCL initially treated with CHOP± R who subsequently relapsed were included. All patients received DHAP or ICE salvage chemotherapy without rituximab followed by ASCT. All patients received BEAM conditioning chemotherapy without rituximab and none received rituximab post transplantation. Results: Eighty-eight patients (67%) received CHOP as initial therapy and 42 (33%) received R-CHOP. The median age was 56 years (range 21–77), 83 patients were male and 47 were female. Based on the International Prognostic Index (IPI) at the time of ASCT, 66 patients were low risk, 48 low-intermediate and 16 high-intermediate risk. With a median follow up of 22 months, there was no difference in the time to progression (p=0.31) or overall survival (p=0.22) between patients initially treated with R-CHOP and those treated with CHOP. When patients >60 years (n=49) treated either with CHOP or R-CHOP were analyzed, there was no difference in overall survival (p=0.52). However, in patients ≤ 60 years (n=81) there was a significantly poorer survival (p=0.03) for those treated with R-CHOP when compared to those treated with CHOP. This finding remained significant in a multivariate analysis (p=0.03). Conclusions: Patients ≤60 years with DLBCL who receive R-CHOP as initial treatment may be less likely to be successfully treated with ASCT at the point of relapse when compared to those treated with CHOP alone. This finding should be confirmed in a larger multicenter patient cohort. No significant financial relationships to disclose.
Construction, characterization, and mammalian expression of an immunotoxin consisting of ranpirnase (Rap) fused to a humanized anti-EGP-1 antibody, hRS7, as a potential therapeutic for prostate cancer
Authors: Sailaja Vanama, Puja Sapra, Hans J. Hansen, Ivan D. Horak, Chien-Hsing Chang, David M. Goldenberg
Journal: Cancer Research (2005)

679  Introduction: We describe construction, expression and characterization of a novel immunotoxin involving ranpirnase (Rap), an amphibian ribonuclease (RNase) isolated from the oocytes of Rana pipiens (Northern leopard frog), as the toxin moiety, and an internalizing humanized monoclonal antibody (mAb), hRS7, as the tumor-targeting agent. Rap is a single-chain protein of 104 amino acids (MW ∼12 kDa) exhibiting cytostatic and cytotoxic effects on a variety of tumor cell lines in vitro as well as antitumor activity in vivo. Previous studies indicated that cytotoxicity of Rap is enhanced more than 10,000-fold when the enzyme is chemically conjugated to an internalizing antibody. The murine mAb RS7-3G11 reacts with epithelial glycoprotein-1 (EGP-1). A high frequency of EGP-1 expression has been observed in a variety of tumor types, including lung, stomach, bladder, breast, ovary, uterus and prostate, with limited presence on normal human tissues. The intended therapeutic application for the immunotoxin is prostate cancer. The Rap molecule contains a putative glycosylation site N69-V70-T71, and when it is expressed in mammalian cultures, the Rap molecule is glycosylated. To obtain a non-glycosylated form of Rap, N69 has been mutated to Q. The basic design of the immunotoxin, 2L-Rap(N69Q)-hRS7-γ1, consists of two N69Q-mutated Rap molecules, each connected via a flexible linker to the N-terminus of one light chain of the hRS7 antibody. Methods: The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hRS7. Sp2/0 mouse myeloma cells were transfected, and positive clones were identified by ELISA screening. The fusion protein was purified by protein A column chromatography and characterized by a variety of techniques, including SE-HPLC, SDS-PAGE, and an in vitro transcription translation (IVTT) assay using the luciferase reporter system. Results: The purified protein was shown to be a single peak by SE-HPLC. The EC50 of RNase activity, as measured by the IVTT assay, was 1400 pM for 2L-Rap(N69Q)-hRS7 and 30 pM for free Rap. Conclusion: A novel immunotoxin for targeting prostate cancer has been developed and expressed in a mammalian system. This will now permit testing in appropriate prostate cancer systems.
Abstract 14635: Highly Purified Human iPS Cell Derived Cardiomyocyte Cell Sheet Improves Cardiac Function Through Electromechanical Integration in Porcine Ischemic Cardiomyopathy Model - a Preclinical Trial for Myocardial Regeneration Therapy
Authors: Masashi Kawamura, Shigeru Miyagawa, Kenji Miki, Atsuhiro Saito, Taichi Sakaguchi, Hiroyuki Nishi, Yasushi Yoshikawa, Satsuki Fukushima, Shunsuke Saito, Takahiro Higuchi, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2011)

Introduction Human iPS cell derived cardiomyocytes(hiPS-CMs) is a promising cell source in regenerating myocardium. However, several issues exist for clinical translation, including how to obtain a...
HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation
Authors: Seok-Rae Park, Hong Zan, Zsuzsanna Pal, Jinsong Zhang, Ahmed Al-Qahtani, Egest J Pone, Zhenming Xu, Thach Mai, Paolo Casali
Journal: Nature Immunology (2009)
Ciba Foundation colloquia on endocrinology. Volume 14: Immunoassay of hormones.
Authors: G. E. W. Wolstenholme, Margaret P. Cameron
Journal: JAMA (1963)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor
Authors: Jessy J. Alexander, Lee D. Chaves, Anthony Chang, Shruti Dighe, Alexander Jacob, Richard J. Quigg
Journal: Cellular and Molecular Immunology (2015)

Activation of complement generates C5a which leads to signaling through C5aR1. This is tightly controlled, including by the plasma proteins factor H (FH) and carboxypeptidase N. Here we studied a chronic serum sickness (CSS) model of glomerulonephritis (GN) in which there is an active humoral immune response, formation of glomerular immune complexes (ICs), and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH−/− mice compared to wild-type FH+/+ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance.
Abstract 16773: Exercise Tolerance and Vo2 Are Improved in Patients Undergoing Fontan Conversion with Arrhythmia Surgery
Authors: Sabrina Tsao, Gregory Webster, Kendra Ward, Wayne H Franklin, Barbara J Deal
Journal: Circulation (2011)

Background: Exercise tolerance in Fontan patients is known to decline with advancing age. The impact of improving right atrial flow dynamics and eliminating anti-arrhythmic medications on exercise tolerance is not known. Hypothesis: Successful Fontan conversion with arrhythmia surgery results in improvement in exercise tolerance over time. Methods: We reviewed data on patients who underwent Fontan conversion at our center since 1994. Fontan conversion surgery included arrhythmia surgery with pacemaker implantation. Exercise duration, peak HR, respiratory quotient, VO2, age at most recent exercise test and postoperative interval were recorded. Continuous variables were compared using two-tailed t-test method. Results: Fontan conversion with arrhythmia surgery has been performed on 132 pts at our institution. Pre-operative exercise testing was performed in 88 pts, with paired follow-up exercise data available on 29 pts. The mean age at Fontan conversion was 22.7 years. The mean interval from surgery to the most recent exercise stress test was 4.8 years (0.5-14.1 yrs). The mean exercise duration at baseline was 69% predicted for age and improved to a mean of 78% predicted for age at follow-up (p=0.02, mean duration in minutes: 6.9 at baseline, 8 at follow-up). The mean VO2 predicted for age improved from 53% to 64% (p&lt;0.01, mean VO2 in ml/kg/min increased from 22.3 to 25.8) (see graph below for results). No significant change was seen in peak heart rate (148 vs 150 bpm, p=NS). Conclusions: In contrast to an expected decline in exercise tolerance with age in Fontan patients, successful Fontan conversion with arrhythmia surgery results in improvement in exercise endurance and oxygen consumption over a 5 yr follow-up period. Data was only available in a limited subset of patients undergoing Fontan conversion. These findings suggest that aggressive measures to improve hemodynamics in Fontan patients can result in improvement in functional status in adulthood.
Abstract 2471: Comparison of the Angiographic and Clinical Benefit of Different Types of Drug-Eluting Stents when Used Instead of Bare-Metal Stents
Authors: Raul Moreno, Cristina Fernandez, Luis Calvo, Angel Sanchez-Recalde, Guillermo Galeote, Fernando Alfonso, Rosa Sanchez-Aquino, Rosana Hernandez, Jose L Lopez-Sendon, Carlos Macaya
Journal: Circulation (2006)

There are different types of drug-eluting stents (DES) commercially available in Europe. The aim was to compare the angiographic and clinical benefit of these different types of DES when used inste...
Abstract 2423: B-type Natriuretic Peptide Upregulates Erythropoietin Receptor Gene Expression via Protein Kinase G in Heart Failure
Authors: Yoshiaki Ohyama, Toru Tanaka, Takehisa Shimizu, Hiroshi Doi, Norimichi Koitabashi, Tatsuya Iso, Akihiko Nakano, Masashi Arai, Masahiko Kurabayashi
Journal: Circulation (2008)

Backgroud: Recent studies demonstrated non-hematopoietical effects of Erythropoietin (Epo) and its receptor (EpoR) in a variety of tissues including cardiovascular system. Epo treatment improves cardiac function in patients with heart failure and reduces infarct size after ischemia/reperfusion injury in the heart. However, little attention has been paid for the endogenous regulatory mechanisms regulating EpoR expression. In this study, we hypothesize that B-type natriuretic peptide upregulates EpoR gene expression in failing heart. Methods and Results: Wister rats underwent transverse aortic constriction surgery to induce hypertrophy. RT-PCR analyses of those rats showed that EpoR mRNA levels were increased in the left ventricle and positively correlated with the levels of BNP mRNA (n=10, r=0.67, p&lt;0.05). Next we examined the expression of EpoR in human failing heart by using autopsy specimens and found that EpoR mRNA levels were significantly elevated in patients with dilated cardiomyopathy compared with those in normal heart. Immunohistochemistry of endomyocardial biopsy specimens of failing heart (n=54) showed that EpoR mRNA levels were correlated with severity of cardiac dysfunction estimated by diameter of cardiac chambers, pathomorphology, serum BNP concentration and functional class of New York Heart Association. Interestingly, stimulation of cultured neonatal rat cardiac myocytes with BNP, but not with hypertrophic reagents including endothelin I, angiotensin II and norepinephrine, significantly increased the EpoR mRNA levels in a time-dependent manner. Overexpression of cGMP-dependent protein kinase (PKG) increased EpoR transcript in cultured cardiac myocytes. BNP-induced EpoR expression was abrogated in the presence of KT5823, a specific inhibitor for PKG. Conclusion: These results suggest a role for BNP in mediating an induction of EpoR expression in failing myocardium and indicate that the cardiac EpoR gene is a target of cGMP/PKG signaling.
Final report of a randomized phase II study of docetaxel/oxaliplatin (DO) and docetaxel (D) in previously treated non-small cell lung cancer (NSCLC) patients (pts). A novel design, Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 019)
Authors: O. Belvedere, A. Follador, C. Rossetto, A. M. Sibau, C. Defferrari, M. Aita, S. Meduri, G. Fasola, T. Ceschia, F. Grossi
Journal: Journal of Clinical Oncology (2009)

e19010 Background: No combination regimen has proven superior to single agent chemotherapy as 2nd-line treatment for NSCLC. The absence of cross-resistance with cisplatin/carboplatin, favorable toxicity profile, along with both pre-clinical and clinical evidence of activity make O a good candidate for combination with D as 2nd-line therapy of NSCLC. We evaluated the activity of DO in this setting using a novel phase II trial design. Methods: This multicenter, non-comparative randomized phase II trial evaluated the activity of D (75 mg/m2 d1) and O (70 mg/m2 d2) every 3 weeks in previously treated NSCLC pts; the comparator arm was D (75 mg/m2 d1 every 3 weeks). This one-stage, three-outcome phase II trial design (Sargent, Control Clin Trials 2001) had 21 evaluable pts/arm. All had histologically confirmed NSCLC that progressed during/after platinum-based chemotherapy. Primary endpoint was response rate; secondary endpoints were toxicity, time to progression (TTP), 1-yr survival. Results: Fifty pts were enrolled. Pts characteristics: M/F, 76/24%; median age 62 yrs (range 43–69); ECOG PS 0/1, 36/64%; adenocarcinoma/other, 36/64%. With 48 pts evaluable, partial response was seen in 20% and 8% of pts; stable disease in 52% and 32% and progressive disease in 24% and 56% for DO and D, respectively; 1 pt was inevaluable due to early death (D arm). Main grade 3–4 toxicities were: neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhea 12% and 4% for DO and D, respectively. Median TTP was 4.9 and 1.8 months, median survival 10.9 and 6.9 months, and 1-yr survival 41% and 16% for DO and D, respectively. Conclusions: This study shows how novel phase II trial designs enrolling a limited number of pts may help identify promising regimens for subsequent study in phase III trials. The level of activity for DO we observed satisfied the pre-defined study primary endpoint and warrants further evaluation of this combination as 2nd-line therapy for NSCLC. Protocol developed at the 6 th FECS/AACR/ASCO Workshop on Methods in Clinical Cancer Research, Flims 2004, with Professors Marc Buyse and Chris Twelves. [Table: see text]
泌尿外科学基础知识（二）：常见的儿科泌尿系疾病
Authors: Prem, Hugh, Whitfield, Chris, Dawson, 张宁（译）
Journal: BMJ (2006)

许多儿科泌尿疾病患者会寻找内科专家看病，本文简述了一些常见的这类疾病，包括包茎、丸下降不全，回缩丸、膀胱输尿管反流、尿道下裂、新生儿肾积水、肾盂输尿管连接部梗阻和一些常见类型的肿瘤。
Multiplex analysis of apoptosis signaling pathways
Authors: Rick Wiese, Joseph Hwang, Jehangir Mistry
Journal: Cancer Research (2008)

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

4365 

Under normal physiological conditions, such as embryonic development and tissue homeostasis, apoptotic processing allows for the removal of individual or select groups of cells in a deliberate and controlled manner. Apoptosis is also initiated as a protective mechanism for the removal of cells which have incurred significant DNA damage. Conversely, the dysregulation of apoptotic processes plays a central role in the pathology of cancer. Aberrant apoptotic signaling allows for the survival and clonal expansion of neoplastic cells. Numerous signaling pathways and proteins are involved in apoptosis. The ability to monitor the abundance of these specific apoptotic pathway member proteins is necessary for a thorough understanding of the processes these pathways affect. To facilitate the analysis of several apoptosis pathway member proteins, we have constructed several Luminex xMAP® based immunoassays. Assays were developed to analyze the apoptosis-related proteins: cleaved PARP, phosphorylated Histone H2A.X (pS139), phosphorylated Histone H2B (pS14), total and phosphorylated Bad (pS136), total and active Caspase 8 and GAPDH. Assay conditions were further optimized for the simultaneous analysis of active Caspase 3, cleaved PARP, phosphorylated Histone H2A.X and GAPDH in a single assay. Presented here are the results of several experiments designed to fully characterize these immunoassays using the Jurkat human T cell line treated with anisomycin or the A431 human carcinoma cell line treated with EGF (phosphorylated Bad). Assay response for both treated and non-treated cellular lysates was determined to be both specific and analyte concentration dependant. Western blotting experiments corroborate the results observed for the developed assays. These results demonstrate that the apoptosis analysis tools we have designed are an effective and efficient method to monitor critical constituents of the apoptotic pathway.
Proliferation and viability studies of hibiscus sabdariffa, momordica charantia, and cabbage on PC-3 cells
Authors: Melissa Redwood, Tiffany Taylor, Monica Frazier, Pamela Leggett-Robinson
Journal: Cancer Research (2008)

4371  African-Caribbean men in Jamaica and African-American men in the US have the highest occurrence of prostate cancer in the world. Diets high in fat are thought to be one of the many causes of prostate cancer. Although the Jamaican diet is relatively healthy, including foods high in antioxidants, they still have some of the highest prostate cancer incidence and mortality rates. This is thought to be due in part to the lack of treatment and late stage at diagnosis. Treatments available for prostate cancer include expensive treatments such as radiotherapy and anti-androgens which are not affordable for many, especially the Jamaicans. Moreover, no curative therapies are available for those with metastatic cancer. To this end, more affordable and curative therapies are needed. In an attempt to address these issues, compounds found in vegetables and fruits commonly consumed by these groups are examined for their ability to elicit anticarcinogenic activities against the metastatic prostate cancer cell line PC-3. The studies presented here explore the anticarcinogenic activities of cabbage, a common vegetable consumed by African-Americans, and the fruit of two Jamaican plants, Hibiscus sabdariffa (Jamaican sorrel) and Momordica charantia (Jamaican cerasse). Cabbages are known to contain isothiocyanates which have anticarcinogenic activity. However, few studies, if any, have been performed on the use of these extracts and teas as treatment for end stage prostate cancer. We therefore hypothesize that treatment of PC-3 cells with extracts and teas from cabbage and the Jamaican plants sorrel and cerasse will cause a loss in viability and proliferation of these cells. The fruit and leaves of the Jamaican sorrel and cerasse plants are also known to contain some medicinal compounds as they are typically prepared and consumed as teas to cure common ailments. In this study, the viability and proliferation of PC-3 cells treated with various concentrations of Hibiscus sabdariffa and Momordica charantia tea preparations, and cabbage extracts was examined using MTT and Trypan blue analysis. Laboratory studies show a dose-dependent inhibition in the growth and viability of PC-3 cells treated with cabbage extracts of more than 50%. Preliminary studies of the Jamaican cerasse and sorrel teas show similar results. Studies are underway which look at apoptotic markers such as Bcl-2 and caspases for activation of apoptosis in treated cells. Together, these data support the potential use of these extracts and teas for the treatment of prostate cancer.
Abstract 5502: Adiponectin Mediates the Effects of Atherogenic Risk Profile on the Coronary Microcirculation in Patients with Idiopathic Lv Systolic Dysfunction
Authors: Daniela Giannessi, Chiara Caselli, Silvia Del Ry, Maristella Maltinti, Manuela Cabiati, Nader Abraham, Antonio L’Abbate, Danilo Neglia
Journal: Circulation (2008)

Purpose. Adiponectin (ADN), a biologically active protein produced by the adipose tissue, has protective vascular effects. Accordingly, ADN plasma levels are reduced in patients with coronary artery disease (CAD) while in heart failure ADN tends to increase. We hypothesized that ADN plasma levels could mediate the effects of atherogenic risk profile on the coronary microcirculation of patients with early LV systolic dysfunction (ILVDys) not secondary to established CAD. Methods. Plasma ADN was measured in 55 patients (age 59±1 yrs, 36 males, BMI 26.9±0.49 Kg/m 2 , mean±sem) with angiographically normal coronary arteries, LV systolic dysfunction (LVEF 39.8±1.3 % range 22–54 %) but without overt heart failure (NYHA class I–II) and in 40 age- and BMI-matched healthy controls by using a specific Elisa (Linco Res). BMI, cholesterol and glucose profiles were assessed in all. In a subset of 25 patients coronary microvascular function was studied by PET and 13 N-Ammonia as a flow tracer. Myocardial blood flow (MBF) was measured at rest and during i.v. dipyridamole (Dip) (0.56 mg/Kg in 4 min). Results. ADN was 6.6±0.34 μg/ml in controls and 10.9±0.85 in ILVDys patients (p&lt;0.001). In patients ADN levels were inversely related with BMI (p=0.009) and directly related with age (p=0.007), HDL Cholesterol (p=0.003) and MBF Dip (0.020). Patients showing more severe coronary microvascular dysfunction (MBF Dip&lt;1.42 ml/min/g, median value in patients) had significantly depressed ADN (9.7±2.3 vs 13.7±1.6, p=0.021) as compared with the remaining patients. Conclusions. This is the first study which associates adiponectin plasma levels with atherogenic risk profile and coronary microvascular function in patients with idiopathic LV dysfunction. These results suggest that adiponectin signal is strongly involved in mediating coronary vascular function independently of the presence of overt CAD or heart failure.