tbuckley/cabot-search huggingface dataset:
Abstract 3669: IDH mutant glial cell resistance to natural killer cell cytotoxicity
Authors: Xiaoran Zhang, Yigang Chang, Aofei Li, Joseph C. Glorioso, Paola Grandi, Mike Lotze, Nduka Amankulor
Journal: Cancer Research (2014)

Abstract Mutations in IDH 1 and 2 are common in gliomas. Methylation-related epigenetic repression of gene expression is a feature of IDH mutant (IDHmut) tumors. Epigenetic repression of NK cell ligands is a common occurrence in cancer, but it is unknown if this occurs in gliomas. Here, we demonstrate transcriptional repression of NKG2D activating ligands (NKG2DLs) in IDHmut tumors, and correlate this with decreased susceptibility to natural killer (NK) cell-mediated cytolysis in vitro We compared IDHmut and IDHwt gene expression values for annotated immune response genes and examined NKG2DL HM450 mean methylation values in glioma patients using TCGA data. cDNA was synthesized from cultured IDHwt or IDHmut astrocytes. NKG2DL expression was assayed using primers for NKG2D ligands ULBP1, ULBP2, ULBP3 and RAET1G. IDHwt astrocytes, U87 cells and IDHmut astrocytes were cultured with activated NK cells. Cytotoxicity was measured by flow cytometry. mRNA expression values for NKG2DLs ULBP1 and ULBP3 were significantly reduced in IDHmut gliomas. Conversely, methylation values were significantly increased. NKG2DL hierarchical clustering of gene expression of shows genotype-based expression clusters. IDHmt astrocytes expressed a two to eight-fold reduction in the relative gene expression of NKG2DLs compared with IDHwt astrocyte. Cytotoxicity is significantly lower in IDHmut astrocytes/NK cell co-cultures compared with IDHmut/NK or U87/NK co-cultures. Our data demonstrates evidence for the transcriptional repression of NKG2DLs in IDHmut gliomas in silico and in vitro. Reduced NKG2D levels in IDHmut cells correlates with impaired NK-mediated cytotoxicity and suggests a role for NK cell resistance in IDH mutant tumors. Further studies are in progress to utilize HSV vectors that express ULBP3 to determine whether restoration of ULBP3 expression in cancer cells will enhance susceptibility to NK activation and tumor cell killing. Results of these experiments will be reported. Citation Format: Xiaoran Zhang, Yigang Chang, Aofei Li, Joseph C. Glorioso, Paola Grandi, Mike Lotze, Nduka Amankulor. IDH mutant glial cell resistance to natural killer cell cytotoxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3669. doi:10.1158/1538-7445.AM2014-3669
Improved results after preoperative concurrent chemotherapy and high dose radiation therapy in selected cases with stage III N2 lung cancer
Authors: Kalliopi Athanassiadi, Evangelos Balis, Nectarios Alevizopoulos, Dimitris Lioumpas, Maria-Kalliopi Konstantinidou, Iakovos Ttofi, Irini Mavromati, Argini Psevdi, Lucilla Comis, Despina Violidaki, Dimitra Rondogianni, Ion Bellenis
Journal: European Respiratory Journal (2012)

OBJECTIVE :  Optimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The use of neoadjuvant chemoradiotherapy can present challenges in the perioperative management of patients undergoing lung resection for non-small cell lung cancer. Preoperative chemoradiotherapy may reduce pulmonary function, and can result in significant fibrosis around key anatomic structures, making dissection difficult and hazardous.  METHODS: This is a retrospective study of 40 consecutive patients with T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 2005 through December 2011. Induction chemotherapy consisted of cisplatin, and etoposide; and concurrent radiotherapy to a mean of 59.3 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation.  RESULTS: Twenty-five patients were submitted to pneumonectomy, simple or intrapericardial one, 10 to lobectomies and 5 either to segmentectomies or atypical resection. R0 resection was achieved in all cases. The overall operative mortality rate was 2.5% (one died in the lobectomy group). No important morbidity was noted and the overall hospital stay ranged from 7 to 14 days.  CONCLUSION: Chemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can be performed with low mortality and morbidity and might lead to improved overall and disease-free survival.
A Novel Effective and Safe Consolidation for Patients Over 60 Years with Acute Myeloid Leukemia
Authors: Wolfgang R. Sperr, Maria Piribauer, Friedrich Wimazal, Christa Fonatsch, Renate Thalhammer-Scherrer, Ilse Schwarzinger, Klaus Geissler, Paul Knöbl, Ulrich Jäger, Klaus Lechner, Peter Valent
Journal: Clinical Cancer Research (2004)

Abstract Purpose: High-dose intermittent cytarabine is an effective postremission treatment for patients with acute myeloid leukemia (AML). This regimen is a safe approach in patients &amp;lt; 60 years but produced severe neurotoxicity in the elderly. Experimental Design: We have established a dose-reduced age-adapted consolidation using intermediate dose (IDAC; 2 × 1 g/m2 i.v., days 1, 3, and 5) for AML patients ≥ 60 years. Forty-seven de novo AML patients in complete remission (CR; median age, 70 years) were scheduled to receive four consolidation cycles of IDAC. Results: In 25 of 47 patients (53%), all four cycles were administered: 9 (19%) received three cycles; 7 (15%) received two cycles; and 6 patients (12%) one cycle. Treatment was well tolerated without neurotoxicity. The median number of days with severe neutropenia (absolute neutrophil count &amp;lt; 500/μl) was 9. Neutropenic fever occurred in 22 of 47 patients (49%) during the first cycle, in 24 of 41 (60%) during the second, in 15 of 34 (44%) during the third, and in 18 of 25 (72%) during the fourth cycle. Only 1 patient died during consolidation (cardiac failure). The median overall survival, disease-free survival, and continuous CR were 10.6, 15.5, and 15.9 months, respectively. The probability of overall survival, disease-free survival, and continuous CR at 5 years were 18, 22, and 30%, respectively. Conclusions: IDAC is a safe and effective postremission therapy for elderly patients with AML.
Maternal weight, gestational weight gain and preschool wheezing: the Generation R Study
Authors: Elisabeth T.M. Leermakers, Agnes M.M. Sonnenschein-van der Voort, Romy Gaillard, Albert Hofman, Johan C. de Jongste, Vincent W.V. Jaddoe, Liesbeth Duijts
Journal: European Respiratory Journal (2013)

We studied the associations of maternal pre-pregnancy body mass index and gestational weight gain with risks of preschool wheezing in offspring and explored the role of growth, infectious and atopic mechanisms. This substudy of 4656 children was embedded in a population-based birth cohort. Information about maternal pre-pregnancy weight, gestational weight gain and wheezing at the ages of 1–4 years was obtained by either physical measurements or questionnaires. Among mothers with a history of asthma or atopy, maternal pre-pregnancy obesity was associated with an overall increased risk of preschool wheezing (odds ratio 1.47, 95% confidence interval 1.12–1.95). Also, each standard deviation increase of gestational weight gain was associated with an increased overall risk of preschool wheezing (1.09, 1.04–1.14), was independent of pre-pregnancy body mass index and was not different between mothers with and without a history of asthma or atopy. Child’s growth, respiratory tract infections or eczema did not alter the results. Mothers with pre-pregnancy obesity and a history of asthma or atopy, and mothers with higher gestational weight gain showed higher risks of wheezing in their offspring. These associations could not be explained by growth, infectious or atopic mechanisms. Further research is needed to identify underlying mechanisms and long-term consequences.
Relationship of alterations in splenic clearance function and microcirculation to host defense in acute rodent malaria.
Authors: D J Wyler, T C Quinn, L T Chen
Journal: Journal of Clinical Investigation (1981)

During the course of Plasmodium berghei malaria in the rat, splenic clearance of damaged uninfected erythrocytes (heated or Heinz body-containing) underwent changes strikingly similar to those of infected erythrocytes. Splenic trapping of abnormal erythrocytes was impaired during the period of rising parasitemia but became supernormal just before the onset of resolution of the acute infection. These changes could be related to the development of splenomegaly and alterations in splenic cordal microcirculation during infection. The relative distribution of flow through the cords was decreased during rising parasitemia and was restored before the onset of resolution. Together, our observations support the hypothesis that altered rheologic properties of infected erythrocytes are a major determinant of their removal by the spleen. These data suggest that the alterations in splenic microcirculation that occur during malaria may have important implications for host defense.
The μ Switch Region Tandem Repeats Are Important, but Not Required, for Antibody Class Switch Recombination
Authors: Thomas M. Luby, Carol E. Schrader, Janet Stavnezer, Erik Selsing
Journal: The Journal of Experimental Medicine (2001)

Class switch DNA recombinations change the constant (C) region of the antibody heavy (H) chain expressed by a B cell and thereby change the antibody effector function. Unusual tandemly repeated sequence elements located upstream of H chain gene exons have long been thought to be important in the targeting and/or mechanism of the switch recombination process. We have deleted the entire switch tandem repeat element (S(mu)) from the murine (mu) H chain gene. We find that the S(mu) tandem repeats are not required for class switching in the mouse immunoglobulin H-chain locus, although the efficiency of switching is clearly reduced. Our data demonstrate that sequences outside of the S(mu) tandem repeats must be capable of directing the class switch mechanism. The maintenance of the highly repeated S(mu) element during evolution appears to reflect selection for a highly efficient switching process rather than selection for a required sequence element.
Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade Compared With Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Intervention
Authors: A. Michael Lincoff, John A. Bittl, Robert A. Harrington, Frederick Feit, Neal S. Kleiman, J. Daniel Jackman, Ian J. Sarembock, David J. Cohen, Douglas Spriggs, Ramin Ebrahimi, Gadi Keren, Jeffrey Carr, Eric A. Cohen, Amadeo Betriu, Walter Desmet, Dean J. Kereiakes, Wolfgang Rutsch, Robert G. Wilcox, Pim J. de Feyter, Alec Vahanian, Eric J. Topol
Journal: JAMA (2003)

Context The direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI). Objective To determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications. Design, Setting, and Participants The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)–2 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. Interventions Patients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. Main Outcome Measures The primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization. Results Provisional Gp IIb/IIIa blockade was administered to 7.2% of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P = .32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P = .40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P &amp;amp;lt;.001). Conclusions Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.
Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin
Authors: Soma Jyonouchi, Valsamma Abraham, Jordan S. Orange, Jonathan M. Spergel, Laura Gober, Emily Dudek, Rushani Saltzman, Kim E. Nichols, Antonella Cianferoni
Journal: Journal of Allergy and Clinical Immunology (2011)
Postmastectomy Radiation and Mortality in Women With T1-2 Node-Positive Breast Cancer
Authors: Benjamin D. Smith, Grace L. Smith, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2005)

To determine the relationship between postmastectomy radiotherapy (PMRT) and mortality in a population-based cohort of women with T1-2 node-positive breast cancer.Using data from the Surveillance, Epidemiology, and End Results program, we identified 18,038 women with T1-2 node-positive invasive breast cancer who were treated with mastectomy between 1988 and 1995. The relationship between PMRT and mortality was determined using proportional hazards multivariate modeling and propensity score matched case-control analysis.Median follow-up was 8.1 years. Only 2,648 women (15%) received PMRT. After adjusting for covariates, PMRT use was not associated with mortality (hazard ratio [HR] = 0.96; 95% CI, 0.90 to 1.03). However, the interaction term for PMRT use and number of involved regional lymph nodes was significant (P = .002), suggesting that, above a certain threshold of involved nodes, a mortality benefit from PMRT may exist. Adjusted analysis stratified by number of involved nodes revealed that patients with seven or more involved nodes treated with PMRT experienced a significant reduction in all-cause (HR = 0.84; 95% CI, 0.76 to 0.93) and cause-specific mortality (HR = 0.86; 95% CI, 0.77 to 0.96). Propensity score matched case-control analysis confirmed that PMRT was associated with reduced mortality only in the subset of patients with seven or more involved nodes (HR = 0.81; 95% CI, 0.73 to 0.91 for all-cause mortality; and HR = 0.82; 95% CI, 0.72 to 0.93 for cause-specific mortality).For women with T1-2 breast cancer, PMRT is associated with a 15% to 20% relative reduction in mortality for patients with seven or more involved regional lymph nodes.
Randomized Phase III Study of Matrix Metalloproteinase Inhibitor BMS-275291 in Combination With Paclitaxel and Carboplatin in Advanced Non-Small-Cell Lung Cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18
Authors: Natasha B. Leighl, Luis Paz-Ares, Jean-Yves Douillard, Christian Peschel, Andrew Arnold, Alain Depierre, Armando Santoro, Daniel C. Betticher, Ulrich Gatzemeier, Jacek Jassem, Jeffrey Crawford, Dongsheng Tu, Andrea Bezjak, Jeffrey S. Humphrey, Maurizio Voi, Susan Galbraith, Katherine Hann, Lesley Seymour, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2005)

Purpose To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non–small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m 2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.
Cytokine Milieu Tends Toward Inflammation in Type 2 Diabetes
Authors: Katherine Esposito, Francesco Nappo, Francesco Giugliano, Carmen Di Palo, Myriam Ciotola, Michelangela Barbieri, Giuseppe Paolisso, Dario Giugliano
Journal: Diabetes Care (2003)

It has been postulated that type 2 diabetes is a manifestation of the inflammatory host response (1). Increased inflammatory activity is believed to play a critical role in development of atherogenesis and to predispose established atherosclerotic plaques to rupture (2). Interleukin (IL)-8 is a potent chemoattractant (chemokine) and induces recruitment of neutrophils and T-cells into the subendothelial space, as well as adhesion of monocytes to endothelium (3). IL-18 is a potent proinflammatory cytokine reported to play a role in plaque destabilization and to predict cardiovascular death in patients with coronary artery disease (4). Adiponectin is an …
An audit of the incidence and treatment of buried internal gastrostomy fixators
Authors: A. Young, L. Leedham
Journal: Gut (2011)

<h3>Introduction</h3> Buried gastrostomy bumper can lead to infection, inability to administer feeds/medications, peritonitis and admission to hospital. In some cases surgical removal in this vulnerable patient group is the only option. Regular review of community patients can identify this problem at an early stage leading to successful endoscopic intervention. Buried bumper syndrome (BBS) occurs when the gastrostomy internal bumper is pulled up against the gastric mucosa with too much force eroding into the mucosa, which overgrow, until the bumper becomes partially or completely buried. Flow through the tube is obstructed and feed may leak back around it onto the skin. We have developed a novel endoscopic technique to free the buried bumper. Under endoscopic control, an oesophageal dilatation balloon is passed through the tube from the outside and seen endoscopically emerging into the stomach. Inflating the balloon while it is still partly within the PEG tube dilates a passage through the over-grown mucosa and also stiffens the tube so that it could be pushed back into the stomach <h3>Methods Aim</h3> To audit the incidence of BBS and the results of endoscopic intervention. A 3 year audit of all PEGs placed at the Royal Liverpool Hospital was performed to examine the incidence of BBS and the results of our novel endoscopic intervention <h3>Results</h3> Over a three year period 329 PEGs have been inserted. Of these 15 (4.5%) have developed BBS In 2007, 6 patients had buried bumpers; 4 could not be freed endoscopically and required surgical intervention. In 2 cases the bumper was successfully freed.. In 2008, a 87.5% success rate (n=7) was achieved using the method described above. In 2009 there were no reported cases of buried bumper. In 2010, successful freeing of the bumper was achieved on first attempt in 62.5% with an overall success rate of 75% after a second attempt at the procedure in one case. <h3>Conclusion</h3> BBS occurs in 4.5 % of patients Of these patients 68% can be freed by the technique we have developed with minimal complications.
Myelodysplastic syndrome treatment with danazol and cis‐retinoic acid
Authors: Louis Letendre, Ralph Levitt, Robert V. Pierre, Georgene Schroeder, James A. Krook, James E. Mailliard, Roscoe F. Morton, Loren K. Tschetter
Journal: American Journal of Hematology (1995)

Abstract We prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13‐Cis‐Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression. Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13‐CRA, 1 response among 20 cases that received high dose 13‐CRA, and 1 partial response and 1 minor response to Danazol among 34 cases. Neither 13‐Cis‐Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use. © 1995 Wiley‐Liss, Inc.
Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells.
Authors: C D Pauza, J E Galindo, D D Richman
Journal: The Journal of Experimental Medicine (1990)

High levels of unintegrated viral DNA accumulate during human immunodeficiency virus type 1 (HIV-1) infection of CEM T cells. Reinfection of already infected cells is required to attain these levels and reinfection also promotes the development of HIV-induced cytopathology. Rates of virus production, however, are independent of the accumulation of unintegrated viral DNA. Neutralizing antibody added soon after infection reduced viral DNA levels without appreciably affecting the production of cell-free viral p24 antigen or reverse transcriptase activity. Only 50 pM AZT were required to reduce the accumulation of unintegrated viral DNA by 50% in contrast to the 25 nM required to inhibit virus production by 50%. Cytopathology, as measured by number of syncytia in infected cell cultures, was correlated with highly elevated levels of unintegrated viral DNA. The minimal levels of unintegrated viral DNA present constitutively in the persistently infected HCEM cell line were consonant with the absence of cytopathic effects in these cells. These data demonstrate that inhibiting the reinfection of already infected cells modulates cytopathic HIV-1 infection to a form that is persistent and noncytopathic.