tbuckley/cabot-search huggingface dataset:
A DNA Vaccine Targeting Survivin Combines Apoptosis with Suppression of Angiogenesis in Lung Tumor Eradication
Authors: Rong Xiang, Noriko Mizutani, Yunping Luo, Claudia Chiodoni, He Zhou, Masato Mizutani, Yi Ba, Juergen C. Becker, Ralph A. Reisfeld
Journal: Cancer Research (2005)

A novel strategy achieved the eradication of lung tumor metastases by joint suppression of angiogenesis in the tumor neovasculature and induction of tumor cell apoptosis. This was accomplished by CTLs induced by a DNA vaccine encoding secretory chemokine CCL21 and the inhibitor of apoptosis protein survivin, overexpressed by both proliferating endothelial cells in the tumor vasculature and tumor cells. Oral delivery of this DNA vaccine by doubly attenuated Salmonella typhimurium (dam(-) and AroA(-)) to such secondary lymphoid organs as Peyer's patches in the small intestine, elicited marked activation of antigen-presenting dendritic cells, and an effective CD8(+)T cell immune response against the survivin self-antigen. This resulted in eradication or suppression of pulmonary metastases of non-small cell lung carcinoma in both prophylactic and therapeutic settings in C57BL/6J mice. Moreover, the suppression of angiogenesis induced by the vaccine did not impair wound healing or fertility of treated mice. It is anticipated that such novel DNA vaccines will aid in the rational design of future strategies for the prevention and treatment of cancer.
High Plasma Osteopontin Level and Its Relationship with Interleukin-12–mediated Type 1 T Helper Cell Response in Tuberculosis
Authors: Yoshinobu Koguchi, Kazuyoshi Kawakami, Kaori Uezu, Kiyoyasu Fukushima, Sigeyuki Kon, Masahiro Maeda, Atsushi Nakamoto, Isoko Owan, Mutsuo Kuba, Norifumi Kudeken, Masato Azuma, Satomi Yara, Takashi Shinzato, Futoshi Higa, Masao Tateyama, Jun-Ichi Kadota, Hiroshi Mukae, Shigeru Kohno, Toshimitsu Uede, Atsushi Saito
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Osteopontin (OPN, also known as Eta-1), a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in granulomatous lesions caused by Mycobacterium tuberculosis infection. In the present study, we compared plasma concentrations of OPN in patients with active pulmonary tuberculosis with those of healthy control subjects and patients with sarcoidosis, another disease associated with granuloma formation. Plasma OPN levels were significantly higher in patients with tuberculosis (n = 48) than in control subjects (n = 34) and patients with sarcoidosis (n = 20). OPN levels correlated well with severity of pulmonary tuberculosis, as indicated by the size of lung lesions on chest X-ray films. Furthermore, chemotherapy resulted in a significant fall in plasma OPN levels. In patients with tuberculosis, plasma OPN concentrations correlated significantly with those of interleukin (IL)-12. In vitro experiments showed that OPN production by peripheral blood mononuclear cells infected with Mycobacterium bovis bacillus Calmette–Guérin preceded the synthesis of IL-12 and interferon-γ and that the neutralizing anti-OPN monoclonal antibody significantly reduced the production of IL-12 and interferon-γ. Our results suggest that OPN may be involved in the pathologic process associated with active pulmonary tuberculosis by inducing IL-12–mediated type 1 T helper cell responses.
Role of Macrophage Targeting in the Antitumor Activity of Trabectedin
Authors: Giovanni Germano, Roberta Frapolli, Cristina Belgiovine, Achille Anselmo, Samantha Pesce, Manuela Liguori, Eugenio Erba, Sarah Uboldi, Massimo Zucchetti, Fabio Pasqualini, Manuela Nebuloni, Nico van Rooijen, Roberta Mortarini, Luca Beltrame, Sergio Marchini, Ilaria Fuso Nerini, Roberta Sanfilippo, Paolo G. Casali, Silvana Pilotti, Carlos M. Galmarini, Andrea Anichini, Alberto Mantovani, Maurizio D’Incalci, Paola Allavena
Journal: Cancer Cell (2013)
Can GOLD Stage 0 Provide Information of Prognostic Value in Chronic Obstructive Pulmonary Disease?
Authors: Jørgen Vestbo, Peter Lange
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

In the recently published guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) for chronic obstructive pulmonary disease (COPD), the staging system included a Stage 0 for subjects without airways obstruction but with respiratory symptoms, denoting these subjects “at risk” for COPD. Our aim was to validate this staging approach using data from three surveys in The Copenhagen City Heart Study, in which a sample of the general population was examined at baseline and in which, after 5 and 15 years, spirometry was performed at all surveys. Criteria for GOLD Stage 0 was fulfilled by 5.8% of the total adult population and 7.2% of smokers. After 5 and 15 years, 13.2 and 20.5%, respectively, of smokers with GOLD Stage 0 had developed COPD fulfilling criteria for GOLD Stage 1 or worse. This was the case for 11.6 and 18.5%, respectively, of smokers without respiratory symptoms. Further analyses using multivariate logistic regression analysis confirmed that GOLD Stage 0 was not identifying subsequent airways obstruction. When analyzing FEV1 decline, Stage 0 carried a risk of excess decline. GOLD Stage 0 was not a stable feature, which may explain the lack of predictive value. In the Western world, smoking is still in itself the most important indicator of risk of COPD, and alternative markers of susceptibility in the population must be investigated.
Genetic Loci Modulate Macrophage Activity and Glomerular Damage in Experimental Glomerulonephritis
Authors: Jacques Behmoaras, Jennifer Smith, Zelpha D'Souza, Gurjeet Bhangal, Ratana Chawanasuntoropoj, Frederick W.K. Tam, Charles D. Pusey, Timothy J. Aitman, H. Terence Cook
Journal: Journal of the American Society of Nephrology (2010)

The Wistar Kyoto (WKY) rat is uniquely susceptible to experimentally induced crescentic glomerulonephritis. Two major quantitative trait loci (QTLs) on chromosomes 13 (Crgn1) and 16 (Crgn2) with logarithm of odds >8, as well as five other loci (Crgn3 through 7), largely explain this genetic susceptibility. To understand further the effects of Crgn1 and Crgn2, we generated a double-congenic strain by introgressing these loci from glomerulonephritis-resistant Lewis rats onto the WKY genetic background. Induction of nephrotoxic nephritis in the double-congenic rats (WKY.LCrgn1,2) produced markedly fewer glomerular crescents, reduced macrophage infiltration, and decreased expression of glomerular TNF-α and inducible nitric oxide synthase expression compared with control animals. Bone marrow and kidney transplantation studies between parental and WKY.LCrgn1,2 strains, together with in vitro experiments, demonstrated that Crgn1 and Crgn2 contribute exclusively to circulating cell-related glomerular injury by regulating macrophage infiltration and activation. The residual genetic susceptibility to crescentic glomerulonephritis in WKY.LCrgn1,2 rats associated with macrophage activity (especially with enhanced metalloelastase expression) rather than macrophage infiltration. Taken together, these results demonstrate that a genetic influence on macrophage activation, rather than number, determines glomerular damage in immune-mediated glomerulonephritis.
Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors
Authors: Luis G. Paz-Ares, Carlos Gomez-Roca, Jean-Pierre Delord, Andres Cervantes, Ben Markman, Jesus Corral, Jean-Charles Soria, Yann Bergé, Desamparados Roda, Fiona Russell-Yarde, Simon Hollingsworth, José Baselga, Pablo Umana, Luigi Manenti, Josep Tabernero
Journal: Journal of Clinical Oncology (2011)

We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G(1) anti-epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity.Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design.No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patients), infusion-related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs were rash (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), paronychia (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 exposure increased greater than proportionally over the 50- to 400-mg dose range (with greater than proportional decline in clearance) and approximately dose proportionally above 400 mg (where clearance plateaued). A marked reduction in circulating natural killer cells and increased infiltration of immune effector cells into skin rash were seen. Clinical efficacy included one complete response and two partial responses in patients with colorectal cancer (including one with KRAS mutation) and disease stabilization in 27 patients.RG7160 had an acceptable safety profile with manageable AEs and demonstrated promising efficacy in this heavily pretreated patient cohort. On the basis of modeling of available PK parameters, the RG7160 dose selected for part two of this study is 1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.
Multicenter Randomized Phase II Study of Weekly or Twice-Weekly Bortezomib Plus Rituximab in Patients With Relapsed or Refractory Follicular or Marginal-Zone B-Cell Lymphoma
Authors: Sven de Vos, André Goy, Shaker R. Dakhil, Mansoor N. Saleh, Peter McLaughlin, Robert Belt, Christopher R. Flowers, Mark Knapp, Lowell Hart, Dipti Patel-Donnelly, Martha Glenn, Stephanie A. Gregory, Charles Holladay, Tracy Zhang, Anthony L. Boral
Journal: Journal of Clinical Oncology (2009)

Purpose To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20 + follicular lymphoma (FL) or marginal-zone lymphoma. Patients and Methods Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m 2 twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m 2 weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m 2 weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using oncologist/radiologist-adjudicated data from independent radiology review and investigator assessment. Results Eighty-one patients (arm A, n = 41; arm B, n = 40) were enrolled. Dose-intensity was higher in arm A; mean total bortezomib received was similar between arms (18.5 and 17.1 mg/m 2 ). In arm A, ORR was 49% (14% complete response [CR]/CR unconfirmed [CRu]), median TTP was 7.0 months, and median DOR was not reached. In arm B, ORR was 43% (10% CR/CRu), and median TTP/DOR were 10.0/9.3 months. The weekly combination regimen seemed better tolerated. Grade 3 or worse adverse events seemed more common in arm A (54%) versus arm B (35%), including thrombocytopenia (10% v 0%) and peripheral neuropathy (10% v 5%), but diarrhea seemed less frequent (7% v 15%). No grade 4 toxicities were reported in arm B. Conclusion Both bortezomib plus rituximab regimens seem feasible in relapsed or refractory indolent lymphomas. The more convenient weekly combination regimen is being compared with single-agent rituximab in an ongoing phase III study in relapsed FL.
Immunologic Changes in Human Albumin Exposed to Toluene Diisocyanate (TDI) Vapor: Differences Compared with Liquid TDI Exposure and Association with IgE/IgG Binding and TDI Asthma
Authors: Y. Ye, S. Kim, S. Lee, H. Park, C.A. Redlich, A.V. Wisnewski
Journal: Journal of Allergy and Clinical Immunology (2006)
Response to Tricyclic Antidepressants: Independent of Gender?
Authors: Tamar Wohlfarth, Jitschak G. Storosum, André J.A. Elferink, Barbara J. van Zwieten, Annemarie Fouwels, Wim van den Brink
Journal: American Journal of Psychiatry (2004)

The authors examined gender differences in response to tricyclic antidepressants.A total of 30 randomized, placebo-controlled trials that included 3,886 patients (1,555 men and 2,331 women), submitted between 1979 and 1991 in order to obtain marketing authorization, were reviewed. Gender differences in response to treatment were tested in various multiple regression models using a variety of response definitions.Different response definitions all pointed to no gender difference in the efficacy of tricyclic antidepressants. The estimated effect size was similar for women younger and older than age 50 and for men.Tricyclic antidepressant response is independent of gender.
Development of chronic colitis is dependent on the cytokine MIF
Authors: Ype P. de Jong, Ana C. Abadia-Molina, Abhay R. Satoskar, Kareem Clarke, Svend T. Rietdijk, William A. Faubion, Emiko Mizoguchi, Christine N. Metz, Mazen Al Sahli, Tessa ten Hove, Andrew C. Keates, Jodi B. Lubetsky, Richard J. Farrell, Pierre Michetti, Sander J. van Deventer, Elias Lolis, John R. David, Atul K. Bhan, Cox Terhorst
Journal: Nature Immunology (2001)
Structural Constraints and Emergence of Sequence Patterns in Protein Evolution
Authors: Gustavo Parisi, Julián Echave
Journal: Molecular Biology and Evolution (2001)

The aim of this work was to study the relationship between structure conservation and sequence divergence in protein evolution. To this end, we developed a model of structurally constrained protein evolution (SCPE) in which trial sequences, generated by random mutations at gene level, are selected against departure from a reference three-dimensional structure. Since at the mutational level SCPE is completely unbiased, any emergent sequence pattern will be due exclusively to structural constraints. In this first report, it is shown that SCPE correctly predicts the characteristic hexapeptide motif of the left-handed parallel β helix (LβH) domain of UDP-N-acetylglucosamine acyltransferases (LpxA).
Children in South Asia Have Higher Body Mass–Adjusted Blood Pressure Levels Than White Children in the United States
Authors: Tazeen H. Jafar, Muhammad Islam, Neil Poulter, Juanita Hatcher, Christopher H. Schmid, Andrew S. Levey, Nish Chaturvedi
Journal: Circulation (2005)

Blood pressure during childhood is an established predictor of adult blood pressure, which in turn increases mortality as a result of cardiovascular disease. Adult South Asian populations are particularly predisposed to cardiovascular disease compared with whites, but the prevalence of high blood pressure and determinants of blood pressure in South Asian children have not been explored or compared with those of white children.Analyses were performed on 5641 South Asian children 5 to 14 years old included in the nationally representative National Health Survey of Pakistan (NHSP) (1990-1994) and on 4756 white children 5 to 14 years old included in Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994). Anthropometric measurements were obtained. Blood pressure was measured twice in the seated position with a mercury sphygmomanometer and an appropriate-size cuff. High blood pressure was defined as a systolic or diastolic blood pressure level that was > or =95th percentile of age-, sex-, and height-percentile-specific reference level for the US population. Mean body mass index (BMI)-adjusted blood pressure values were compared among children in 2 data sets by use of linear regression analysis. The overall prevalence (95% CI) of high blood pressure in South Asian children 5 to 14 years old was 12.2% (11.3% to 13.1%): 15.8% (14.5% to 17.1%) in boys and 8.7% (7.6% to 9.8%) in girls. This is in sharp contrast with the predicted 5% prevalence of high blood pressure in children in the United States (P<0.001). The mean BMI-adjusted systolic blood pressure levels (SD) were 100 (11) versus 99 (11) mm Hg (P<0.001), and diastolic blood pressure levels (SD) were 63 (10) versus 52 (12) mm Hg (P<0.001) in NHSP versus NHANES III, respectively.South Asian children have higher body-mass-adjusted blood pressure levels than white children in the United States. Further studies are needed to determine factors responsible for these differences. Immediate attention is needed to address high blood pressure and its risk factors in native South Asian children.
Thirty years of surgery for carcinoma of the bronchus.
Authors: J R Belcher
Journal: Thorax (1983)

A study has been made of 8781 patients with bronchial carcinoma who were operated on by seven surgeons in England during the years 1949-80. There were 3865 pneumonectomies, 3790 lobectomies, and 1126 thoracotomies. During this period the operative mortality has fallen. Neither the resection rate nor the proportion of lobectomies bears any relation to the survival rate in any series. There has been remarkable similarity between the various survival rates in that the difference at five years was only 1.3% (25.5-26.8%) and at 10 years 4.2% (13.6-17.8%). These figures are reflected in reports published worldwide, where there is also great similarity between the results. If the improvement in operative mortality is excluded, there has been no improvement in the survival rates in the last thirty years.
Insulin-like Growth Factor Pathway Genetic Polymorphisms, Circulating IGF1 and IGFBP3, and Prostate Cancer Survival
Authors: Yin Cao, Sara Lindström, Fredrick Schumacher, Victoria Stevens, Demetrius Albanes, Sonja Berndt, Heiner Boeing, H. Bas Bueno-de-Mesquita, Federico Canzian, Saioa Chamosa, Stephen Chanock, W. Ryan Diver, Susan Gapstur, J. Michael Gaziano, Edward Giovannucci, Christopher Haiman, Brian Henderson, Mattias Johansson, Loïc Le Marchand, Domenico Palli, Bernard Rosner, Afshan Siddiq, Meir Stampfer, Daniel Stram, Rulla Tamimi, Ruth Travis, Dimitrios Trichopoulos, Walter C.:: ea eef a fc b fa b:: Willett, Meredith Yeager, Peter Kraft, Ann Hsing, Michael Pollak, Xihong Lin, Jing Ma
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundThe insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown. MethodsAmong 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality.We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing.In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality.All statistical tests were two-sided. ResultsThe IGF signaling pathway was associated with PCa mortality (P = .03),and IGF2-AS and SSTR2 were the main contributors (both P = .04).In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P trend less than .05,but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections.Two were in linkage disequilibrium (r 2 = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r 2 = 0.03).The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P trend = .003)for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P trend < .001)for rs4366464.rs4366464 remained statistically significant after correction for all SNPs (P trend.corr= .04).Prediagnostic IGF1 (HR highest vs lowest quartile = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% CI = 0.65 to 1.34) levels were not associated with PCa mortality. ConclusionsThe IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival.
Local-global interactions and the role of mesoscopic (intermediate-range) elements in brain dynamics
Authors: Walter J. Freeman, Robert Kozma
Journal: Behavioral and Brain Sciences (2000)

A unifing theory of spatiotemporal brain dynamics should incorporate multiple spatial and temporal scales. Between the microscopic (local) and macroscopic (global) components proposed by Nunez, mesoscopic (intermediate-range) elements should be integral parts of models. The corresponding mathematical formalism requires tools of nonlinear dynamics and the use of aperiodic (chaotic) attractors. Some relations between local-mesoscopic and mesoscopic-global components are outlined.
Attenuation of Junctional Adhesion Molecule-A Is a Contributing Factor for Breast Cancer Cell Invasion
Authors: Meghna U. Naik, Tejal U. Naik, Arthur T. Suckow, Melinda K. Duncan, Ulhas P. Naik
Journal: Cancer Research (2008)

Abstract The metastatic potential of cancer cells is directly attributed to their ability to invade through the extracellular matrix. The mechanisms regulating this cellular invasiveness are poorly understood. Here, we show that junctional adhesion molecule A (JAM-A), a tight junction protein, is a key negative regulator of cell migration and invasion. JAM-A is robustly expressed in normal human mammary epithelium, and its expression is down-regulated in metastatic breast cancer tumors. In breast cancer cell lines, an inverse relationship between JAM-A expression and the ability of these cells to migrate on a collagen matrix was observed, which correlates with the known ability of these cells to metastasize. The T47D and MCF-7 cells, which migrate least, are found to express high levels of JAM-A, whereas the more migratory MDA-MB-468 cells have lower levels of JAM-A on the cell surface. MDA-MB-231 cells, which are highly migratory, express the least amount of JAM-A. Overexpression of JAM-A in MDA-MB-231 cells inhibited both migration and invasion through collagen gels. Furthermore, knockdown of JAM-A using short interfering RNAs enhanced the invasiveness of MDA-MB-231 cells as well as T47D cells. The ability of JAM-A to attenuate cell invasion correlated with the formation of increased numbers of focal adhesions and the formation of functional tight junctions. These results show for the first time that an immunoglobulin superfamily cell adhesion protein expressed at tight junctions could serve as a key negative regulator of breast cancer cell invasion and possibly metastasis. Furthermore, loss of JAM-A could be used as a biomarker for aggressive breast cancer. [Cancer Res 2008;68(7):2194–203]
Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006
Authors: M. Kaufmann, G. von Minckwitz, H.D. Bear, A. Buzdar, P. McGale, H. Bonnefoi, M. Colleoni, C. Denkert, W. Eiermann, R. Jackesz, A. Makris, W. Miller, J.-Y. Pierga, V. Semiglazov, A. Schneeweiss, R. Souchon, V. Stearns, M. Untch, S. Loibl
Journal: Annals of Oncology (2007)