tbuckley/cabot-search huggingface dataset:
Phase I study of high-dose bi-weekly gemcitabine at a constant rate infusion (CRI) without growth factor support in advanced solid tumors, including prior standard gemcitabine treated patients
Authors: J. Bellmunt, J. M. Trigo, I. Garcia-Ribas, J. M. Roca, S. Galtes, A. Perez-Romero, J. J. de la Cruz, J. M. Tabernero, E. Alba, J. Baselga
Journal: Journal of Clinical Oncology (2005)

2067 Background:Phosphorylation of gemcitabine by deoxycytidine kinase is the rate-limiting step in the accumulation of the active triphosphate metabolite. This enzyme is saturable and the optimal infusion dose rate that maximizes amount of gemcitabine triphosphate is 10 mg/m2/min. Previous experience of weekly gemcitabine at this CRI produced a maximum tolerated dose (MTD) close to the already recommended 30-minute infusion. We are investigating the MTD of gemcitabine at a CRI in patients with solid tumors using a biweekly regimen. Methods: Metastatic patients failing standard therapy (1 or no prior chemotherapy including standard 30-minute gemcitabine) were eligible. Gemcitabine was infused at a CRI of 10 mg/m2/minute every 2 weeks starting at 2,400 mg/m2 with 9 predefined dose-level (DL). In the absence of dose-limiting toxicity (DLT) dose was increased 600 mg/m2 at each DL. Results: Twenty patients (6 female, 14 male); median age 54 (range 38–74); ECOG 0 (10), 1 (10); diagnoses: cholangiocarcinoma (3), unknown primary (2), pancreas (2), bladder (2), head and neck (2), soft-tissue sarcoma (2), cervix (2), prostate (2),breast (2) and kidney (1) received a total of 89 cycles (range 1–17). Up to now MTD has not been reached at dose level 6. Main non-hematologic toxicity was grade 2 alopecia in all patients and grade 3 astenia in 6 patients. Grade 3–4 anemia and neutropenia ocurred in 4 (20%) and 11 (55%) of patients, with no febrile neutropenia. Objective responses (PR) have been observed in 4 patients: unknown primary, cholangiocarcinoma, bladder,and prostate cancer. In 2 patients after previous gemcitabine treatment. Conclusions: Biweekly CRI of gemcitabine is feasible and can be given safely up to a dose of 5400 mg/m2 in 9 hours infusion every 15 days without growth factor support. Activity has been seen in patients pretreated with gemcitabine. MTD has not been reached. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Abstract 5461 In vivo Knockdown of Aortic Nicotinic Acetylcholine Receptor Alpha1 (nAChR{alpha}1) Diminishes Aortic Atherosclerosis and Valve Calcification
Authors: Guoqiang Zhang, Kelly A Kernan, Alison Thomas, Yanyuan Su, Yi Zheng, Renee C LeBoeuf, Allison A Eddy
Journal: Circulation (2009)

Urokinase plasminogen activator (uPA) contributes to atherosclerosis, restenosis and vascular remodeling. We have recently identified nAChR α 1 as a functional cell receptor for uPA in addition to its classic receptor, uPAR. Here, we test the hypothesis that nAChR α 1 plays a role in the pathogenesis of atherosclerosis. C57BL/6J  ApoE  −/−  mice (male) were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA ( pScr ) or siRNA ( pSir2 ) for nAChR α 1 was then injected into the mice (n=15) using an aortic hydrodynamic gene transfer protocol. Three mice from each group were sacrificed 7 days after DNA injection to confirm the nAChR α 1 gene silencing. The rest of the mice continued on the Western diet for an additional 16 wks. Aortas were harvested for paraffin-embedding (aorta root), protein (ascending aorta and aortic arch) and RNA (descending aorta) (n=8). Whole aortas were isolated for oil red staining in 4 mice of each group. The nAChR α 1 was highly up-regulated in aortic atherosclerotic lesions. Knockdown of the nAChR α 1 gene was achieved as early as day 7 (76%↓) after DNA injection, and aortic nAChR α 1 in  pSir2 -treated mice remained lower (78%↓) at 16 wks compared to the  pScr  (n=8,  P  α 1 reduction resulted in less severe aortic atheroslcerosis at 16 wks. The ratio of the intimal/medial thickness (I/M ratio) was smaller in the nAChR α 1-silenced aortas (3.1±1.8 versus 8.4±1.4,  pSir2  versus  pScr , n=8,  P  α SMA+ myofibroblasts (80%↓) in the neointima of the  pSir2 -treated mice compared to the  pScr  (both  P  β 1 and  α SMA mRNA levels were down-regulated by 80% and 72% respectively in the nAChR α 1-silenced aortas ( pSir2 vs pScr ; n=5, both  P  α 1 is a ligand-gated Ca 2+  channel that may be associated with osteopathic responses in aortic intimal myofibroblasts, aortic calcification was evaluated with the Von Kossa staining. The calcification was most prominent in the aortic valves; a 41% reduction in area stained was observed in the  pSir2 -treated mice ( pSir2 vs pScr ; n=8  P  α 1 gene plays a significant role at the artery wall and reducing its expression serves to reduce aortic plaque development and valve calcification.  This research has received full or partial funding support from the American Heart Association, National Center.
HPV-FASTER: broadening the scope for prevention of HPV-related cancer
Authors: F. Xavier Bosch, Claudia Robles, Mireia Díaz, Marc Arbyn, Iacopo Baussano, Christine Clavel, Guglielmo Ronco, Joakim Dillner, Matti Lehtinen, Karl-Ulrich Petry, Mario Poljak, Susanne K. Kjaer, Chris J. L. M. Meijer, Suzanne M. Garland, Jorge Salmerón, Xavier Castellsagué, Laia Bruni, Silvia de Sanjosé, Jack Cuzick
Journal: Nature Reviews Clinical Oncology (2015)
Mortality Risk With Mirtazapine and Estimating Suicide Risk
Authors: Arif Khan, James Faucett, Walter A. Brown
Journal: JAMA Psychiatry (2015)

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 Psychiatry 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 Psychiatry journal
The effect of zidovudine on neuropsychiatric measures in HIV-infected men
Authors: J M Gorman, R Mayeux, Y Stern, J B Williams, J Rabkin, R R Goetz, A A Ehrhardt
Journal: American Journal of Psychiatry (1993)

The authors examined the effects of zidovudine on neuropsychiatric measures, at three assessment points separated by 6 months, in 25 HIV-positive men who took zidovudine for at least 6 months and a comparison group of 25 HIV-positive men with similar CD4+ T cell counts who had never taken zidovudine. Zidovudine had no statistically significant effect except for a slight improvement in Global Assessment of Functioning scale score. In this small group of subjects there was little benefit but also little evidence of CNS toxicity from zidovudine.
Comparing gene expression of histologically normal colon mucosa distant and adjacent to colorectal cancer.
Authors: Joern Kamradt, Janine Einspahr, Sean Davis, Sarah L. Anzick, David S. Alberts, Robert Krouse, Anil R. Prasad, Paul Meltzer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5655 

Purpose: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. The progression of CRC through a series of clinical and histopathological stages is well described. A defining characteristic of the molecular pathology of CRC is genetic instability. Whether caused by chromosomal instability, microsatellite instability or CpG-island-hypermethylation, genetic aberrations may result in altered gene expression. We sought to determine whether gene expression changes already occur in histologically normal mucosa adjacent to CRCs. Therefore we analyzed a sample set containing mucosa biopsied adjacent to and distant from a CRC as well as the tumor itself using microarray technology. Material and Methods: Tissue sample trios (tumor, 1cm adjacent and 10cm distant) were collected from 23 patients who underwent colonic surgery because of diagnosed CRC. According to UICC classification 4 tumors were stage I, 9 stage II, 6 stage III and 4 stage IV. Two tumors were villous adenoma with high-grade dysplasia. 14 tumors were located in the left colon, the remaining were in the right colon. RNA was isolated according to standard protocols. All samples were hybridized against a common reference on 34580 70mer oligonucleotide arrays (Qiagen Human Genome Oligo Set Version 3). Additionally, 1cm and 10cm adjacent samples of each patient were also hybridized in a direct comparison design on the same array platform. Several genes found to be differentially expressed were validated by quantitative real-time PCR. Results: Comparing normal mucosa with corresponding tumor tissue 5075 genes showed a differential expression (p<0.05, FDR adjusted). Remarkably, 2849 genes had a differential expression between left and right colon in normal mucosa samples. Moreover, direct comparison of 1cm and 10cm adjacent normal mucosa samples revealed 68 genes differentially expressed in these two areas. Only a few of these genes had also an altered expression in tumor compared to normal colon tissue. Conclusions: Gene expression differences between histologically normal colon mucosa samples differing only in their distance from an adjacent tumor is of interest and should be validated in a larger sample set. Whether these molecular changes are caused by the presence of adjacent tumor cells or represent very early steps in CRC pathogenesis is unclear and needs to be evaluated in further studies.
Abstract 3544: Intracellular Calcium Mobilization Enhances the Regenerative Potential of Human Cardiac Progenitor Cells
Authors: Carlos Rondon, Joao Ferreira-Martins, Maria Elena Padin-Iruegas, Derin Tugal, Justin A Korn, Noriko Iwata, Toru Hosoda, Antonella De Angelis, Domenico D'Amario, Konrad Urbanek, David A D'Alessandro, Robert E Michler, Annarosa Leri, Jan Kajstura, Piero Anversa, Marcello Rota
Journal: Circulation (2009)
The mechanism of human angiosarcoma drug resistance
Authors: V. Ravi, D. Henry, S. Chen, M. K. Wong
Journal: Journal of Clinical Oncology (2006)

9567 Background: Angiosarcoma (AS) is a malignant neoplasm of endothelial cells. AS has an extremely poor outcome since it can metastasize widely and rapidly becomes chemoresistant. Understanding the mechanism of this resistance is important not only because of the critical need for new therapeutic strategies in sarcoma, but also since it sheds light on important pathways in endothelial growth that may help understand tumor angiogenesis. Methods/Results: We have established and characterized stable pre-chemotherapy (named B8) and chemotherapy-resistant (named D3) angiosarcoma cell lines from an individual patient with primary (non radiated) breast angiosarcoma prior to initiation of chemotherapy and later after development of resistance to adriamycin, ifosfamide, gemcitabine, docetaxel, paclitaxel, interferon, thalidomide and bevacizumab. D3 cells differ dramatically from B8s in morphology and function. Prechemotherapy B8 cells assume a polygonal morphology reminiscent of native endothelial cells, the D3 cells throw out long processes that span several cell lengths, and do not appear to contact-inhibit. Migration and invasion assays confirm the highly motile nature of these cells. Although it is not surprising that the D3 cells were doxorubicin resistant, we found that unlike the B8 cells, the D3 cells actively transcribe VEGF. In keeping with this, D3 cells are relatively more sensitive to growth inhibition by the anti-VEGF drug bevacizumab than chemonaïve B8 cells. Conclusion: These studies reveal two avenues to target chemoresistant human angiosarcoma; via agents affecting cell migration and those agents that target the VEGF pathway. No significant financial relationships to disclose.
Abstract 20805: Angiogenic and Inflammatory Whole Blood Transcriptional Fingerprint at the Site of Coronary Occlusion in Acute Myocardial Infarction
Authors: olivier muller, Leen Delrue, Michalis Hamilos, Steven Vercauteren, Argyrios Ntalianis, Catalina Trana, Fabio Mangiacapra, Karen Dierickx, Bernard De Bruyne, William Wijns, Atta Behfar, Emanuele Barbato, Andre Terzic, Marc Vanderheyden, Jozef Bartunek
Journal: Circulation (2010)
Percutaneous Implantation of the Edwards SAPIEN Transcatheter Heart Valve for Conduit Failure in the Pulmonary Position
Authors: Damien Kenny, Ziyad M. Hijazi, Saibal Kar, John Rhodes, Michael Mullen, Raj Makkar, Girish Shirali, Mark Fogel, John Fahey, Mary G. Heitschmidt, Christopher Cain
Journal: Journal of the American College of Cardiology (2011)
T1 Mapping for Myocardial Extracellular Volume Measurement by CMR
Authors: Steven K. White, Daniel M. Sado, Marianna Fontana, Sanjay M. Banypersad, Viviana Maestrini, Andrew S. Flett, Stefan K. Piechnik, Matthew D. Robson, Derek J. Hausenloy, Amir M. Sheikh, Philip N. Hawkins, James C. Moon
Journal: JACC. Cardiovascular imaging (2013)
Outcomes in Diabetic and Nondiabetic Patients Treated With Everolimus- or Paclitaxel-Eluting Stents
Authors: Dean J. Kereiakes, Donald E. Cutlip, Robert J. Applegate, John Wang, Manejeh Yaqub, Poornima Sood, Xiaolu Su, Guoping Su, Naim Farhat, Ali Rizvi, Charles A. Simonton, Krishnankutty Sudhir, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Abstract 2597: Aortic Atresia Is Associated with an Inferior Postoperative Systemic, Cerebral and Splanchnic Oxygen Transport Status in Neonates with Hypoplastic Left Heart Syndrome after the Norwood Procedure
Authors: Gencheng Zhang, Glen Van Arsdell, Helen Holtby, Sally Cai, Osman Al Radi, Jia Li
Journal: Circulation (2008)

Aortic atresia (AA) has been identified as a risk factor for mortality after the Norwood procedure. We compared postoperative systemic and regional (cerebral and splanchnic) oxygen transport profiles in neonates with hypoplastic left heart syndrome with or without AA after the Norwood procedure. Systemic oxygen consumption (VO 2 ) was measured using respiratory mass spectrometry postoperatively for 72 hrs in 17 neonates (n=9 in AA group and 8 in non-AA group). Arterial, superior vena cava, and pulmonary venous blood gases and pressures were measured at 2– 4 hr intervals to calculate cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO 2 ) and oxygen extraction ratio (ERO 2 ). Cerebral (ScO 2 ) and splanchnic (SsO 2 ) oxygen saturations were measured using near infrared spectroscopy. The doses of dopamine, vasopressin (up to 0.0008 unit/kg/min), phenoxybenzamine and milrinone were noted. When compared to non-AA group, AA group had lower CO (p=0.03), higher systolic arterial blood pressure (p=0.01) and SVR (p=0.002), lower DO 2 (p=0.07), VO 2 (p=0.003) and ScO 2 during the first 30 to 40 hrs. There was no significant difference in SsO 2 (p=0.12, n=7 in AA group and 3 in non-AA group). Despite a similar ERO 2 (p=0.5), AA group had higher lactate over 72 hrs (p=0.01). AA group received higher doses of vasopressin (p=0.005) and milrinone (p&lt;0.0001), lower doses of dopamine (p=0.07), with similar use of phenoxybenzamine. Furthermore, VO 2 negatively correlated with vasopressin (p=0.05), positively correlated with milrinone (p=0.03) and dopamine (p&lt;0.0001). When including the drugs, the inferior status in all the oxygen transport variables remained, and additionally adversely correlated with vasopressin (p from &lt;0.0001 to 0.06), except for ScO 2 that positively correlated with dopamine, but not with other drugs. Aortic atresia is associated with an inferior status of systemic, cerebral and splanchnic oxygen transport in neonates after the Norwood procedure. Aggressive use of vasopressin worsens systemic and splanchnic oxygen transport status. Postoperative management strategies should be directed to improve both systemic and regional oxygen transport in this special group of patients.
Correlation of acute cocaine-induced changes in local cerebral blood flow with subjective effects
Authors: G D Pearlson, P J Jeffery, G J Harris, C A Ross, M W Fischman, E E Camargo
Journal: American Journal of Psychiatry (1993)

The authors administered 48 mg of intravenous cocaine or placebo to eight abstinent cocaine users in a double-blind, crossover design and examined blood flow using single photon emission computed tomography. Cocaine produced significant decreases in frontal cortical and basal ganglia blood flow; these latter correlated negatively with increases in self-ratings of "rush" and "high." The authors conclude that these local effects are compatible with dopaminergic system involvement.
Human Endothelial Cells in Culture and In Vivo Express on Their Surface All Four Components of the Glycoprotein Ib/IX/V Complex
Authors: Guoxin Wu, David W. Essex, Frank J. Meloni, Toshiro Takafuta, Kingo Fujimura, Barbara A. Konkle, Sandor S. Shapiro
Journal: Blood (1997)

Abstract The platelet glycoprotein Ib (GpIb) complex is composed of four polypeptides: the disulfide-linked GpIbα and GpIbβ and the noncovalently associated GpIX and GpV. GpIbα contains binding sites for von Willebrand factor and for thrombin and mediates platelet adhesion to the subendothelium under conditions of high shear stress. We have previously shown the presence of GpIbα and GpIbβ mRNA and protein in cultured human umbilical vein endothelial cells (HUVECs) as well as the presence of GpIbα mRNA and protein in tonsillar endothelium. We, therefore, probed ECs for the presence of the other components of the GpIb/IX/V complex. We have identified the presence of GpIX and GpV mRNA in cultured HUVEC monolayers. The sequence of HUVEC GpIX cDNA was identical to the previously published human erythroleukemia (HEL) cell GpIX cDNA sequence. Two species of GpV mRNA, one of 3 kb and one of 4.4 kb, were found in HUVECs, whereas HEL cells displayed only the 4.4-kb species and the megakaryocytic cell line CHRF-288 contained only the 3-kb species. We previously showed that EC GpIbα protein is identical in molecular weight to platelet GpIbα. HUVEC GpIbβ, in contrast to its platelet counterpart, has a molecular weight of 50 kD and forms a correspondingly larger disulfide-bonded complex with EC GpIbα. The molecular weights of GpIX and GpV were 22 and 88 kD, respectively, identical to the corresponding platelet polypeptides. Furthermore, we have identified all four components of the complex in tonsillar vessels. Using flow cytometry, we have established that all four polypeptides of the GpIb/IX/V complex are expressed on the surface membranes of cultured HUVECs and adult aortic ECs. Furthermore, using two-color fluorescence, we have shown that all ECs expressing GpIbα also express GpIX and GpV on their surface. The ratio of GpIbα:GpIX:GpV is 1:1:0.5, which is identical to the ratio present in platelets. None of the polypeptides of the GpIb complex could be identified on the surface of human smooth muscle cells or lymphocytes. The presence of all members of the GpIb complex in the EC membrane suggests that this complex may play a role in endothelial function in vivo.
Eyelid Necrosis and Periorbital Necrotizing Fasciitis
Authors: Jan W. Kronish, William M. McLeish
Journal: Ophthalmology (1991)

Necrotizing fasciitis is an uncommon and severe soft tissue infection characterized by cutaneous gangrene, suppurative fasciitis, and vascular thrombosis. The disease is usually preceded by trauma in patients that have systemic problems, most commonly diabetes and alcoholism. Streptococcus pyogenes and Staphylococcus aureus are the most frequent bacterial etiologies; however, combinations of numerous facultative and anaerobic organisms have also been isolated. Involvement of the face and periocular region is rare. A case is presented here, as well as a review of the clinical features of 15 other patients previously described, in whom eyelid necrosis due to periorbital necrotizing fasciitis developed. Early surgical debridement and drainage of necrotic tissues and appropriate parenteral antibiotics are the mainstay of therapy. The mortality rate in patients with periorbital spread was 12.5%, with the prognosis known to be adversely affected by delay in diagnosis and treatment and/or extension of infection from the face to the neck. Reconstruction of the eyelids with skin grafts was necessary in most cases to avoid such complications as cicatricial lid retraction, lid malpositions, and lagophthalmos.
Maintenance of Certification Programs and the Interstate Medical Licensure Compact—Reply
Authors: Paul Teirstein, Eric J. Topol
Journal: JAMA (2015)

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