tbuckley/cabot-search huggingface dataset:
A "fat chance" it's malignant: lipoid pneumonia simulating lung cancer on PET scan
Authors: B D Fox, I Shechtman, D Shitrit, D Bendayan, M R Kramer
Journal: Thorax (2007)

A ''fat chance'' it's malignant: lipoid pneumonia simulating lung cancer on PET scan A 65-year-old man underwent lobectomy following a positron emission tomography (PET) scan showing increased uptake in a nodular lesion in the middle lobe (fig 1).A preoperative transbronchial biopsy specimen demonstrated lipoid pneumonia which was disregarded as a false positive (fig 2).No tumour was seen in the excised lobe.Lipoid pneumonia is caused by aspiration of exogenous oils.It usually causes lung infiltrates but may also assume a nodular form suggesting a tumour. 1 The PET scan may be ''positive'' as a result of metabolic activity of inflammation. 2Physicians should consider lipoid pneumonia in the differential diagnosis of a PET-positive lung lesion to avoid unnecessary surgery.
Combined BRAF (Dabrafenib) and MEK Inhibition (Trametinib) in Patients With <i>BRAF</i><sup>V600</sup>-Mutant Melanoma Experiencing Progression With Single-Agent BRAF Inhibitor
Authors: Douglas B. Johnson, Keith T. Flaherty, Jeffrey S. Weber, Jeffrey R. Infante, Kevin B. Kim, Richard F. Kefford, Omid Hamid, Lynn Schuchter, Jonathan Cebon, William H. Sharfman, Robert R. McWilliams, Mario Sznol, Donald P. Lawrence, Geoffrey T. Gibney, Howard A. Burris, Gerald S. Falchook, Alain Algazi, Karl Lewis, Georgina V. Long, Kiran Patel, Nageatte Ibrahim, Peng Sun, Shonda Little, Elizabeth Cunningham, Jeffrey A. Sosman, Adil Daud, Rene Gonzalez
Journal: Journal of Clinical Oncology (2014)

Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF and MEK inhibition is more effective in BRAF(V600)-mutant melanoma than single-agent BRAF inhibitors. This study assessed the safety and efficacy of dabrafenib and trametinib in patients who had received prior BRAF inhibitor treatment.In this open-label phase I/II study, we evaluated the pharmacology, safety, and efficacy of dabrafenib and trametinib. Here, we report patients treated with combination therapy after disease progression with BRAF inhibitor treatment administered before study enrollment (part B; n = 26) or after cross-over at progression with dabrafenib monotherapy (part C; n = 45).In parts B and C, confirmed objective response rates (ORR) were 15% (95% CI, 4% to 35%) and 13% (95% CI, 5% to 27%), respectively; an additional 50% and 44% experienced stable disease ≥ 8 weeks, respectively. In part C, median progression-free survival (PFS) was 3.6 months (95% CI, 2 to 4), and median overall survival was 11.8 months (95% CI, 8 to 25) from cross-over. Patients who previously received dabrafenib ≥ 6 months had superior outcomes with the combination compared with those treated < 6 months; median PFS was 3.9 (95% CI, 3 to 7) versus 1.8 months (95% CI, 2 to 4; hazard ratio, 0.49; P = .02), and ORR was 26% (95% CI, 10% to 48%) versus 0% (95% CI, 0% to 15%).Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitor-resistant melanoma. This regimen may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy ≥ 6 months but demonstrates minimal efficacy after rapid progression with BRAF inhibitor therapy.
Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia
Authors: Monika Brüggemann, Thorsten Raff, Thomas Flohr, Nicola Gökbuget, Makoto Nakao, Jo Droese, Silke Lüschen, Christiane Pott, Matthias Ritgen, Urban Scheuring, Heinz-August Horst, Eckhard Thiel, Dieter Hoelzer, Claus R. Bartram, Michael Kneba
Journal: Blood (2005)
Leukocyte surface origin of human alpha1-acid glycoprotein (orosomucoid).
Authors: C G Gahmberg, L C Andersson
Journal: The Journal of Experimental Medicine (1978)

Specific antibodies against human alpha1-acid glycoprotein reacted with human lymphocytes, granulocytes, and monocytes. The antigen on the leukocytes is an externally located integral membrane glycoprotein which is made by the cells and has an apparent mol wt of 52,000. It is released from cells in vitro to the culture medium. The mol wt of the soluble fragment is 41,000, which corresponds to that of alpha1-acid glycoprotein in serum and urine. Peptide mapping confirmed that the main part of the cellular membrane antigen consists of alpha1-acid glycoprotein with an additional, probably hydrophobic fragment. This finding may partially explain the increase in the serum levels of alpha1-acid glycoprotein observed in many disorders involving leukocyte proliferation. In addition, the known sequence homology of alpha1-acid glycoprotein with immunoglobulins can now be more easily understood by their origin in similar cell types.
Role of the Estrogen Receptor Coactivator AIB1 (SRC-3) and HER-2/neu in Tamoxifen Resistance in Breast Cancer
Authors: C. K. Osborne, V. Bardou, T. A. Hopp, G. C. Chamness, S. G. Hilsenbeck, S. A. W. Fuqua, J. Wong, D. C. Allred, G. M. Clark, R. Schiff
Journal: JNCI Journal of the National Cancer Institute (2003)

AIB1 (SRC-3) is an estrogen receptor (ER) coactivator that, when overexpressed in cultured cells, can reduce the antagonist activity of tamoxifen-bound ERs. Signaling through the HER-2 receptor pathway activates AIB1 by phosphorylation. To determine whether high AIB1 expression alone or together with HER-2 reduces the effectiveness of tamoxifen in breast cancer patients, we quantified expression of AIB1 and HER-2 in tumors from breast cancer patients with long-term clinical follow-up who received either no adjuvant therapy or adjuvant tamoxifen therapy after breast cancer surgery.AIB1 and HER-2 protein levels in tumors from 316 breast cancer patients were determined using western blot analysis. Molecular variables (e.g., expression of AIB1, ER, progesterone receptor, p53, Bcl-2), tumor characteristics, and patient outcome were assessed using Spearman rank correlation. Disease-free survival (DFS) curves were derived from Kaplan-Meier estimates, and the curves were compared by log-rank tests. The effect of AIB1 on DFS adjusted for other prognostic factors was assessed by multivariable analysis using the Cox proportional hazards model. All statistical tests were two-sided.High AIB1 expression in patients not receiving adjuvant tamoxifen therapy was associated with better prognosis and longer DFS (P =.018, log-rank test). In contrast, for patients who did receive tamoxifen therapy, high AIB1 expression was associated with worse DFS (P =.049, log-rank test), which is indicative of tamoxifen resistance. The test for interaction between AIB1 expression and tamoxifen therapy was statistically significant (P =.004). When expression of AIB1 and HER-2 were considered together, patients whose tumors expressed high levels of both AIB1 and HER-2 had worse outcomes with tamoxifen therapy than all other patients combined (P =.002, log-rank test).The antitumor activity of tamoxifen in patients with breast cancer may be determined, in part, by tumor levels of AIB1 and HER-2. Thus, AIB1 may be an important diagnostic and therapeutic target.
Embryonic Protein Nodal Promotes Breast Cancer Vascularization
Authors: Daniela F. Quail, Logan A. Walsh, Guihua Zhang, Scott D. Findlay, Juan Moreno, Laura Fung, Amber Ablack, John D. Lewis, Susan J. Done, David A. Hess, Lynne-Marie Postovit
Journal: Cancer Research (2012)

Tumor vascularization is requisite for breast cancer progression, and high microvascular density in tumors is a poor prognostic indicator. Patients bearing breast cancers expressing human embryonic stem cell (hESC)-associated genes similarly exhibit high mortality rates, and the expression of embryonic proteins is associated with tumor progression. Here, we show that Nodal, a hESC-associated protein, promotes breast cancer vascularization. We show that high levels of Nodal are positively correlated with high vascular densities in human breast lesions (P = 0.0078). In vitro, we show that Nodal facilitates breast cancer-induced endothelial cell migration and tube formation, largely by upregulating the expression and secretion of proangiogenic factors by breast cancer cells. Using a directed in vivo angiogenesis assay and a chick chorioallantoic membrane assay, we show that Nodal promotes vascular recruitment in vivo. In a clinically relevant in vivo model, whereby Nodal expression was inhibited following tumor formation, we found a significant reduction in tumor vascularization concomitant with elevated hypoxia and tumor necrosis. These findings establish Nodal as a potential target for the treatment of breast cancer angiogenesis and progression.
P1074 THE EFFECT OF LONG-TERM NUCLEOSIDE/TIDE ANALOGUE TREATMENT ON INTRAHEPATIC HBVDNA AND COVALENTLY CLOSED CIRCULAR DNA IN CHRONIC HEPATITIS B PATIENTS
Authors: D.K. Wong, C.-L. Lai, P. Ip, M. Kopaniszen, W.-K. Seto, J. Fung, F.-Y. Huang, R. Wu, C. Cheng, V. Ngai, M.-F. Yuen
Journal: Journal of Hepatology (2014)
The functional spectrum of low-frequency coding variation
Authors: Gabor T Marth, Fuli Yu, Amit R Indap, Kiran Garimella, Simon Gravel, Wen Fung Leong, Chris Tyler-Smith, Matthew Bainbridge, Tom Blackwell, Xiangqun Zheng-Bradley, Yuan Chen, Danny Challis, Laura Clarke, Edward V Ball, Kristian Cibulskis, David N Cooper, Bob Fulton, Chris Hartl, Dan Koboldt, Donna Muzny, Richard Smith, Carrie Sougnez, Chip Stewart, Alistair Ward, Jin Yu, Yali Xue, David Altshuler, Carlos D Bustamante, Andrew G Clark, Mark Daly, Mark DePristo, Paul Flicek, Stacey Gabriel, Elaine Mardis, Aarno Palotie, Richard Gibbs
Journal: Genome biology (2011)

Abstract Background Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. Results The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. Conclusions This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.
Omentin-1 attenuates arterial calcification and bone loss in osteoprotegerin-deficient mice by inhibition of RANKL expression
Authors: H. Xie, P.-L. Xie, X.-P. Wu, S.-M. Chen, H.-D. Zhou, L.-Q. Yuan, Z.-F. Sheng, S.-Y. Tang, X.-H. Luo, E.-Y. Liao
Journal: Cardiovascular Research (2011)

Omentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo. In vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG−/− mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3K–Akt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG−/− mice. These data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway.
Long-Term Results After the Glycoprotein IIb/IIIa Inhibitor Abciximab in Unstable Angina
Authors: J.P. Ottervanger, P. Armstrong, E.S. Barnathan, E. Boersma, J.S. Cooper, E.M. Ohman, S. James, E. Topol, L. Wallentin, M.L. Simoons
Journal: Circulation (2003)

Background— This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. Methods and Results— A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin ( P =0.02), 16.3% versus 12.1% in those with elevated C-reactive protein ( P =0.04). Conclusions— Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality.
Impaired Exercise-Induced Blood Volume in Type 2 Diabetes With or Without Peripheral Arterial Disease Measured by Continuous-Wave Near-Infrared Spectroscopy
Authors: Emile R. Mohler, Gwen Lech, Gregory E. Supple, Hao Wang, Britton Chance
Journal: Diabetes Care (2006)

Diabetes is a significant risk factor for peripheral arterial disease (PAD) and is associated with accelerated atherosclerosis and limb loss. However, the pathophysiology involved in PAD is unclear. This study was conducted to evaluate the hemodynamic response to exercise of patients with and without diabetes and PAD.The hemodynamic response in calf muscles of patients with diabetes, PAD, or both was determined using near-infrared spectroscopy (NIRS). Patients performed both a plantar-flexion and treadmill-walking exercise regimen.Skeletal muscle capillary blood volume expansion during exercise, as measured by NIRS, was significantly impaired in the lower extremities of diabetic patients with a normal ankle-brachial index. The relative deoxygenation and oxygenation recovery times measured by NIRS correlates significantly with the presence of PAD.Patients with diabetes have reduced capillary volume expansion even without PAD. This is likely due to impaired vasodilation secondary to endothelial dysfunction. Further studies are needed to determine whether pharmaceutical intervention improves the blood volume expansion in the diabetic state.
Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota
Authors: Matteo Serino, Elodie Luche, Sandra Gres, Audrey Baylac, Mathieu Bergé, Claire Cenac, Aurelie Waget, Pascale Klopp, Jason Iacovoni, Christophe Klopp, Jerome Mariette, Olivier Bouchez, Jerome Lluch, Francoise Ouarné, Pierre Monsan, Philippe Valet, Christine Roques, Jacques Amar, Anne Bouloumié, Vassilia Théodorou, Remy Burcelin
Journal: Gut (2011)

<h3>Objective</h3> The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. <h3>Methods</h3> The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). <h3>Results</h3> Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. <h3>Conclusions</h3> The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
Nonrandomized Comparison of Primary Chemotherapy and Retroperitoneal Lymph Node Dissection for Clinical Stage IIA and IIB Nonseminomatous Germ Cell Testicular Cancer
Authors: Andrew J. Stephenson, George J. Bosl, Robert J. Motzer, Dean F. Bajorin, Jason P. Stasi, Joel Sheinfeld
Journal: Journal of Clinical Oncology (2007)

PURPOSE Patients with clinical stage (CS) IIA and IIB nonseminomatous germ cell tumor (NSGCT) with adenopathy more than 2 cm, multiple masses, elevated serum tumor markers, or disease outside the primary landing zone have increasingly been recommended to receive primary chemotherapy over time at our institution. The impact of these selection factors on the outcome of patients managed primarily by retroperitoneal lymph node dissection (RPLND) or chemotherapy was examined. PATIENTS AND METHODS Between 1989 and 2002, 252 patients with CS IIA and IIB NSGCT were referred to our institution for initial management, of whom 136 underwent RPLND and 116 received chemotherapy and postchemotherapy RPLND. Patient information was obtained from a prospective RPLND database. Results Proportionately more patients received chemotherapy over time (22% in 1989 to 1993 v 68% in 1999 to 2002), and the relapse-free survival (RFS) subsequently improved from 84% (1989 to 1998) to 98% (1999 to 2002; P = .004) without increasing the proportion who received any chemotherapy (70% v 79%; P = .16). By increasingly selecting patients with adverse features for primary chemotherapy, the RFS after RPLND improved from 78% to 100% (P = .019), but rates of pathologic stage II and retroperitoneal teratoma were unaffected. Retroperitoneal histology and RFS did not change over time for chemotherapy patients. Primary chemotherapy was associated with improved RFS compared with RPLND (98% v 79%; P < .001), but disease-specific survival did not differ significantly (100% v 98%; P = .3). CONCLUSION Patient selection factors have significantly improved the outcome of patients with CS IIA and IIB NSGCT without substantially increasing the proportion of patients exposed to chemotherapy.
Short-Term Use of Estradiol for Depression in Perimenopausal and Postmenopausal Women: A Preliminary Report
Authors: Lee S. Cohen, Claudio N. Soares, Jennifer R. Poitras, Jennifer Prouty, Allison B. Alexander, Jan L. Shifren
Journal: American Journal of Psychiatry (2003)

The authors examined the effect of a 4-week course of estrogen therapy on depression in perimenopausal and postmenopausal women.Twenty-two depressed women who were either perimenopausal (N=10) or postmenopausal (N=12) received open-label treatment with transdermal 17beta-estradiol (100 micro g/day) for 4 weeks. The Montgomery-Asberg Depression Rating Scale and the Beck Depression Inventory were used to assess depressive symptoms, the Greene Climacteric Scale was used to assess menopause-related symptoms, and the Clinical Global Impression (CGI) was used to assess global clinical improvement in these women at baseline and after treatment. Remission of depression was defined as a score <10 on the Montgomery-Asberg Depression Rating Scale and a score </=2 on the CGI at week 4.Remission of depression was noted in eight of the 20 women who completed the study; two of these women were postmenopausal, and six were perimenopausal. Antidepressant response was not associated with severity or subtypes of depression at study entry or with concomitant improvement in menopause-related symptoms.Some perimenopausal women with depression may benefit from short-term use of estrogen therapy, and its role for postmenopausal depressed women warrants further investigation. Antidepressant benefit associated with estrogen therapy may be independent of improvement in physical symptoms.