tbuckley/cabot-search huggingface dataset:
Abstract P170: Neighborhood Socioeconomic Inequalities in Incidence of Acute Myocardial Infarction: a Relative and Absolute Perspective with Reference to Age and Gender.
Authors: Carla Koopman, Louise van Oeffelen, Michiel L Bots, Lenie van Rossem, Ineke van Dis, Peter M Engelfriet, W M Verschuren, Simon Capewell, Ilonca Vaartjes
Journal: Circulation (2012)

Background: Socioeconomic circumstances (SEC) have a profound effect on the risk of having a first coronary heart disease (CHD) event. Yet, information on socioeconomic inequalities across age- and gender-groups is lacking. The objective of this study was to examine socioeconomic inequalities in the incidence of acute myocardial infarction (AMI) in the Netherlands from a relative and absolute perspective, with a particular focus on age and gender. Methods: We identified all patients with a first AMI event from 1997 to 2007 through linked hospital discharge and death records covering the Dutch population (176,715,060 person-years). Relative risks (RR) of AMI incidence were estimated by mean equivalent household income at neighborhood level for strata of age and gender using Poisson regression models. The absolute magnitude of socioeconomic inequalities was estimated by multiplication of population attributable risks (PAR) with the total number of AMI events within the stratified age-gender groups. Results: Between 1997 and 2007, 317,564 people had a first AMI. RR for AMI was 1.34 (95% CI: 1.32 - 1.36) in men and 1.44 (95% CI: 1.42 - 1.47) in women, when comparing the most deprived socioeconomic quintile with the least deprived quintile. The socioeconomic gradient decreased with age. Relative socioeconomic inequalities were most apparent in men under 35 years and in women under 65 years. A total of 50,362 events were attributable to socioeconomic inequalities, with a PAR of 14% in men and 18% in women. The largest burden of absolute AMI events attributable to socioeconomic inequalities was found in men aged 45-74 years, and to a lesser extent in women aged 65-84 years. Conclusion: Neighborhood socioeconomic inequalities are seen for AMI incidence in all age-gender groups in the Netherlands.
Immunohistochemistry (IHC) with EGFR mutation-specific monoclonal antibodies (mAbs) for screening EGFR mutations in non-small cell lung cancer (NSCLC) patients (p).
Authors: S. Simonetti, M. A. Molina, C. Mayo, J. Bertran-Alamillo, T. Moran, S. Benlloch, S. Ramon y Cajal, I. I. Wistuba, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2010)

7570
Abstract 293: Mammalian Target of Rapamycin and Tristetraprolin Regulate Iron Homeostasis in Cardiac Cells
Authors: Marina Bayeva, Arineh Khechaduri, Hossein Ardehali
Journal: Circulation Research (2012)

Introduction: Iron is essential for normal heart function, and disruption of iron homeostasis can lead to cardiomyopathy. However, our understanding of iron regulation on a cellular level is incomplete, with a single model involving iron regulatory proteins (IRP) described to date. Here, we report the existence of a parallel iron regulatory pathway by energy sensor mTOR and inflammatory mediator trsitetraprolin (TTP). Results: To examine the role of energy metabolism in the regulation of cellular iron, we used rapamycin to inhibit mTOR pathway in H9c2 cardiac myoblasts and mouse embryonic fibroblasts (MEFs). Rapamycin treatment significantly elevated cellular iron content through a coordinated reduction in iron import (transferrin receptor, TfR1) and iron export (ferroportin, Fpn1), leading to deceleration of iron flux and net iron accumulation. We found that the primary action of rapamycin was to reduce TfR1 through destabilization of its mRNA. Surprisingly, this effect was not mediated by IRP1/2, the “classical” sensors of cellular iron levels, as TfR1 mRNA levels were significantly reduced by rapamycin even in cells with the genetic knockout of IRP1 and IRP2. In yeast, a tandem zinc finger (TZF) protein Cth2 was found to conserve cellular iron in states of deficiency by preferentially degrading mRNA of non-essential iron-containing proteins thus reducing iron requirements and liberating iron for vital functions. We found that the mammalian TZF protein TTP, an established mediator of inflammation, was greatly induced by iron deficiency, enhanced degradation of iron-containing proteins, and complemented Cth2 deletion in yeast, thus establishing TTP as the functional homolog of Cth2 in mammalian iron regulation. Finally, TTP levels were increased by rapamycin in IRP1/2-independent manner, and genetic knockout of TTP in MEFs significantly reversed the effects of rapamycin on TfR1 mRNA levels and stability. These findings establish TTP as the mediator of iron-regulatory effects of mTOR and provide a novel link between energy metabolism, inflammation and iron regulatory pathways. Conclusions: We identified a novel pathway of cellular iron regulation by mTOR and TTP, which complements the “classical” IRP1/2 model.
Association between single nucleotide polymorphisms (SNPs) of genes involved in spindle assembly checkpoint (SAC) and clinical outcomes in advanced gastric cancer (AGC) patients (pts) treated with taxane-based chemotherapy.
Authors: Shinichi Yamauchi, Satoshi Okazaki, Afsaneh Barzi, Wu Zhang, Dongyun Yang, Shu Cao, Yan Ning, Yu Sunakawa, Stefan Stremitzer, Satoshi Matsusaka, Rita El-khoueiry, Angela Mendez, Anish Parekh, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

79 Background: Taxanes which disrupt the microtubule function and inhibit the process of cell division have shown encouraging activity in the treatment of AGC. Resistance to these agents often becomes a problem in clinical settings and its mechanism hasn’t been dissolved conclusively. SAC is a safety device ensures the proper chromosome segregation in mitosis and is required for taxane-induced cell death. We hypothesized genetic variants in SAC genes may be associated with clinical outcomes in pts with AGC treated with taxane. Methods: Genomic DNA was isolated from blood or tissue samples of 39 U.S. pts (median age 57; median follow-up 6.4 months) for evaluation set and 39 Japanese (JPN) pts (median age 63; median follow-up 9.4 months) for validation set, with AGC treated with taxane. Twenty-five functionally significant SNPs in SAC genes (MAD1, MAD2, BUB3, BUBR1, RAN, TPX2, CDC20, AURKA, AURKB, RCC1, ANAPC10, ANAPC13) were analyzed by PCR-based direct sequencing and evaluated for association with outcomes. Results: In univariate analysis, rs4236271 (MAD1), rs6954673 (MAD1), and rs2064863 (AURKA) showed a significant difference in 6-month (mo) progression-free survival (PFS) rate [(C/C 42%, C/T 12%; HR 2.66, P=0.008), (C/C 75%, C/T or T/T 24%; HR 5.10, P=0.008), and (T/T 50%, T/G 15%, G/G 57%; HR1.55, P=0.046), respectively] and 18-mo overall survival (OS) rate [(C/C 40%, C/T 8%; HR3.69, P&lt;0.001), (C/C 56%, C/T or T/T 19%; HR3.60, P=0.004), and (T/T 59%, T/G 15%, G/G 29%; HR 2.02, P=0.047), respectively] in evaluation set. In multivariate analysis, rs4236271 and rs6954673 remained significant in PFS (HR 7.24, P=0.005, HR 14.49, P=0.015, respectively) and OS (HR 7.39, P=0.001, HR 6.37, P=0.002, respectively). In validation set, rs6954763 showed a significant difference in 18-mo OS rate (C/C 16%, C/T or T/T 47%, HR 3.55, P=0.014), but the impact of C/C genotype on OS in the JPN pts was the opposite to the U.S. pts. Conclusions: These results suggest that MAD1 polymorphisms may serve as a prognostic marker in pts with AGC. Further studies using larger population are needed to corroborate our results.
Transplantation of splenic T-cells from mice vaccinated with lethally-irradiated leukemia cells expressing cell surface GM-CSF prevents leukemia.
Authors: Xiaoyang Ling, Yan Wang, Ralph B. Arlinghaus
Journal: Cancer Research (2006)

5565   Leukemia cells can evade host immune surveillance during leukemia development. This is partially due to leukemic cells expressing weak leukemia-specific antigens and/or due to leukemic cells expressing factors that can impair host immune response. To overcome this tolerance, we transduced the leukemia cells with a cell surface bound GM-CSF. We modified soluble GM-CSF cDNA to a transmembrane-bound form of GM-CSF (tmGM-CSF) and transduced the tmGM-CSF into WEHI-3B leukemia cells by infection with a bi-cistronic tmGM-CSF/ GFP lentivirus. After enrichment of the transduced cells by cell sorting for GFP expression, the resulting cells contained predominantly cell surface bound GM-CSF that was not secreted into the medium. tmGM-CSF expressing WEHI-3B cells were lethally irradiated for use in vaccination. Eight-week old immunocompetent BALB/c mice were vaccinated (sc) in the hind leg with the irradiated cells three times at intervals of seven days (2 × 10e6 cells). Non-vaccinated mice challenged with live WEHI-3B cells died from leukemia after 35 days. All of the vaccinated mice survived for up to 60 days. In order to determine whether cellular immunity is involved in this protection, CD4+ and CD8+ T-cells were depleted after the vaccination. Depletion of CD8+ T cells prevented protection by the vaccine but depletion of CD4+ T cells protected only 20% of mice. The difference between the CD+4 and CD8+ depletion groups is significant (p=0.005). These results indicated that CD8+ T-cells mediated immune response to leukemia cells and play an important role in immune stimulation by the vaccine. Splenic cells were prepared seven days after the last vaccination and 2 × 10e6cells splenic cells were transplanted into non-vaccinated mice one day before the mice were challenged with WEHI-3B leukemia cells (5 × 10e4 cells/mouse). Control mice were transplanted with the splenic cells that isolated from normal non-vaccinated mice. The results showed that 80% of the mice that received splenic cells from vaccinated mice were free leukemia, while all control mice died due to leukemia (p=0.0483). These results indicate that the vaccination of mice with non-viable leukemia cells expressing cell surface-bound GM-CSF can over come the immunotolerance of leukemia cells. Thus, this approach suggests that an ex-vivo manipulation of leukemia cells with cell-surface bound GM-CSF has potential for effective immunotherapy of leukemia.
Results of High-Dose Therapy and Autologous Bone Marrow/Stem Cell Transplantation During Remission in Poor-Risk Intermediate- and High-Grade Lymphoma: International Index High and High-Intermediate Risk Group
Authors: Auayporn Nademanee, Arturo Molina, Margaret R. O'Donnell, Andrew Dagis, David S. Snyder, Pablo Parker, Anthony Stein, Eileen Smith, Ina Planás, Ashwin Kashyap, Ricardo Spielberger, Henry Fung, K.K. Wong, George Somlo, Kim Margolin, Warren Chow, Irena Sniecinski, Nayana Vora, Karl G. Blume, Joyce Niland, Stephen J. Forman
Journal: Blood (1997)
포스터 전시 : 간암을 동반한 간경변 환자에서 발생한 Klebsiella pneumoniae 패혈성 관절염 1예
Authors: 박창환, 이수정, 박정호, 박재홍, 이완식, 주영은, 최성규, 유종선, 김세종
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 패혈성 관절염은 혈행성 전파에 의해서 발생하는 질환으로 최근 당뇨병, 암질환, 만성신부전, 류마치스관절염, 알콜리즘 환자에서 발생이 증가하고 있다. 자발성 세균성 복막염은 간경변 환자에서 흔하면서 심각한 합병증의 하나로 잘 알려져 있지만 간경변 환자에서 발생하는 자발성 패혈성 관절염은 드물게 보고되고 있다. 따라서 보고자들은 간암을 동반한 65세 간경변 환자에서 발생한 Klebsiella pneumoniae 패혈성 관절염 및 복막염을 경험하였기에 보고하는 바이다. 증례: 65세 여자 환자가 우측 슬관절의 통증 및 발적을 주소로 응급실에 내원하였다. 환자는 4년전 간경변을 처음으로 진단받았으며 2년 후에 간암이 발생되어 최근까지 4차례 알콜주사치료를 받은 과거력이 있었다. 내원당시 체온은 38.8℃, 맥박은 분당 84회, 호흡수는 20회, 혈압은 정상범위였다. 신체검사에서 황달을 발견할 수 있었으며 복부진찰에서 복부팽대와 비종대를 확인할 수 있었다. 검사실 성적은 ESR 98 mm/h, 총빌리루빈 7.24 mg/dL, 알부민 2.8 g/dL, PT 3.2 (INR), AFP 189.1 ng/mL이었다. 관절액 천자검사에서 백혈구는 22,900/μL(95% PMNs), 그람 염색에서 그람 음성 세균이 관찰되었고 배양검사에서 Klebsiella pneumoniae로 확인되었다. 혈액배양검사에서도 Klebsiella pneumoniae가 배양되었다. 그러나, 복수천자검사에서 albumin 0.7 g/dL로 SAAG는 2.1이었으며, 중성과립구가 490/μL로 증가되어있었으나 배양검사에서 균주는 자라지않았다. 환자는 cefotaxime 4 g/day사용 후 증상이 호전되었으면 추적 관절액 배양검사에서 균주는 배양되지 않았다. 결론: 저자들은 간암을 동반한 간경변 환자에서 Klebsiella pneumoniae 패혈성 관절염 및 복막염을 경험하였기에 보고하는 바이며, 간경변 환자에서 장내세균에 의한 세균혈증이 복막염외에도 관절강 및 다양한 장기에 감염성 질환을 일으킬 수 있음을 확인할 수 있었다.
Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199
Authors: J. A. Sparano, M. Wang, S. Martino, V. Jones, E. Perez, T. Saphner, A. C. Wolff, G. W. Sledge, W. C. Wood, N. E. Davidson
Journal: Journal of Clinical Oncology (2007)

516 Background: Evidence suggests that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly than every 3 weeks in metastatic breast cancer (BC). Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative BC. All patients received 4 cycles of AC (doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 ) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m 2 every 3 weeks × 4 (P3), (2) paclitaxel 80 mg/m 2 weekly × 12 (P1), (3) docetaxel 100 mg/m 2 every 3 weeks × 4 (D3), or (4) docetaxel 35 mg/m 2 weekly × 12 (D1). The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and secondary comparisons included P3 vs. other arms. The trial had 86% power to detect a 17.5% decrease in disease-free survival (DFS) for either primary comparison, and 80% power to detect a 22% decrease for the secondary comparisons (2-sided nomimal 5% level tests corrected for multiple comparisons). Results: A total of 4,950 eligible patients were accrued. There was no difference in the primary comparisons afer 856 DFS events and 483 deaths after a median follow-up of 46.5 months at the 4th interim analysis ( www.sabcs.org , abstract 48). This is the final pre-specified analysis for the primary comparisons after 1,042 DFS events and 650 deaths (with 1,020 DFS events at this time, to be updated at the meeting). After a median followup of 60.2 months, there remains no significant difference in the hazard ratio (HR) for the taxane (1.02; p=0.73) or schedule (1.07; p=0.30) (as in the first analysis). In secondary comparisons of the standard arm (P3) with the other arms (HR &gt; 1 favoring the experimental arms), the HRs were 1.30 (p = 0.003) for arm P1, 1.24 (p=0.02) for arm D3, and 1.09 (p=0.33) for arm D1. Analysis of interaction by hormone-receptor status will be presented. The incidence of worst grade toxicity (grade 3/4) was 24%/6% for arm P3, 24%/3% for arm P1, 21%/50% for arm D3, and 38%/6% for arm D1. Conclusions: There were no differences in DFS when comparing taxane or schedule overall. DFS was significantly improved in the weekly paclitaxel and every 3-week docetaxel arms compared with the every 3-week paclitaxel arm. [Table: see text]
Effects of Human Adult and Bovine Fetal Serum on Colonial Propagation of Rabbit Cells&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Perry E. Treadwell, John D. Ross
Journal: JNCI Journal of the National Cancer Institute (1962)

Efficient colony formation of a purified line of continuously cultivable epithelial cells of the cottontail rabbit depended on the inclusion of both human adult and bovine fetal serum in medium. Human adult serum favored larger flattened cells, while only small, round cells formed colonies in bovine fetal serum alone. Mixed serum medium yielded many more colonies of each type. Serial isolation and dispersion of morphologically representative colonies and propagation of colonies from such dispersed cells showed that neither serum was adequate for continued cultivation of selected sublines. Cells serially propagated in human serum medium could not generate healthy colonies on return to mixed serum medium; cells serially propagated in bovine fetal serum medium lost colony-forming capacity but recovered it on return to mixed serum medium.
Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure
Authors: Paul M. McKie, John A. Schirger, Sherry L. Benike, Lynn K. Harstad, Joshua P. Slusser, David O. Hodge, Margaret M. Redfield, John C. Burnett, Horng H. Chen
Journal: European Journal of Heart Failure (2016)
Increased plasmatic levels of soluble HLA-G molecules are associated to short-term exposure to fine urban particulate matter
Authors: Gabriella Guarnieri, Roberta Rizzo, Anna Bordin, Maria Cristina Scarpa, Piero Maestrelli
Journal: European Respiratory Journal (2011)

Diesel particles have been shown to enhance allergic inflammation and immune responses. HLA-G is an atypical HLA class I molecule with immuno-modulatory properties. It is detectable in plasma in a soluble form (sHLA-G) and its production is triggered by several stimuli, including IL-10.

The aim of this study is to investigate the effect of short-term exposure to traffic pollution on plasmatic sHLA-G and IL-10 levels in healthy subjects. We recruited 27 healthy non-smoking policemen exposed to traffic and 17 office workers as controls. Before and after the first weekly shift, plasmatic sHLA-G and IL-10, and lung volumes were measured in each subject. sHLA-G and IL-10 levels were analyzed by ELISA. Individual pollution exposure was estimated by airborne PM2.5 and PM10 concentrations.

Pre-shift sHLA-G levels were similar in both groups and increased after shift in the subjects exposed to traffic (before 10.5±1.6 vs after 29.7±4.5 ng/ml, p<0.0001), but not in controls. After shift IL-10 exhibited an opposite trend in the two groups: no changes were observed in the exposed subjects, whereas IL-10 levels decreased in office workers (before 0.7±0.5 vs after 0.5±0.4 pg/ml, p=0.03). sHLA-G cross-shift changes in exposed policemen were positively correlated with PM2.5 levels (rho=0.51, p<0.05). Lung volumes did not exhibit any change after shift in either groups.

In conclusion, short-term exposure to traffic pollution affects the HLA-G system, irrespective of IL-10 levels. The results suggest that fine PM had a systemic immuno-modulatory effect that occurs without changes in lung function.
Correlation between serum PSA and testosterone (T) kinetics in patients (pts) with biochemically relapsed prostate cancer (BRPC) (M0), after local treatment (tx), treated with intermittent androgen deprivation (IAD).
Authors: V. J. Sinibaldi, D. Keizman, M. A. Carducci, S. R. Denmeade, P. Huang, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2010)

4641 Background: IAD is often applied in BRPC (M0) after local tx. Criteria for initiation of androgen deprivation therapy (ADT) and evaluation based on PSA dynamics remain poorly defined. Shortening of PSA doubling time (PSADT) following repeated cycles has been reported as a common development in pts treated by IAD. Aims: To analyze the correlation between serum PSA and T dynamics following discontinuation of ADT in pts with BRPC (M0) treated with IAD. Methods: Data on pts with BRPC (M0) treated by IAD were retrospectively analyzed. Pts received 6-9 months (ms) of ADT discontinued when PSA nadired. Pts were followed with PSA, and T every 3 ms. The PSA threshold for re-tx was defined according to PSADT (PSA range of 10-15ng/ml, 15-20 ng/ml, and 20-30ng/ml for PSADT of ≤3ms, 3-9 ms, and ≥ 9 ms, respectively). IAD was continued until PSA refractoriness or development of progression of disease as evident by physical exams or scans. The correlation between the PSADT and T recovery kinetics was analyzed. Mixed effects model was used to study the dynamic change of PSADT over cycles. Results: Between 1994-2008, 76 pts received a median of 2.3 (range 1-9) cycles of IAD.The median off tx time between cycles was 17.9 mos (2-132 range). With an overall mean follow up time of 50.8 months (6-172 range), 52 pts (68%) remain on tx and 21 pts (28%) have demonstrated evidence of PSA refractoriness (n=6) or radiological progression (n=15). 3 pts (4%) were lost to followup. Evaluation of all PSA values from time of discontinuation (nadir PSA) to re-initiation of ADT (off tx period) demonstrated a progressive shortening of PSADT with each consecutive cycle (decrease of 2.11 ms per unit cycle, p<.0001). However, PSADT calculation including only PSA values obtained after a serum T >100ng/ml was reached, did not show significant shortening over time (decrease of 0.05 ms per unit cycle, p=0.2968). Conclusions: Evaluation of PSADT considering T kinetics in pts treated with IAD may provide more reliable information on PSA dynamics. This approach should be investigated prospectively and, if validated, applied in clinical practice and clinical trials. No significant financial relationships to disclose.
Large rearrangement analysis of <i>MLH1</i> and <i>MSH2</i> in patients undergoing clinical HNPCC testing
Authors: J. P. Tazelaar, N. Tusneem, T. E. Spackman, T. Scholl, L. A. Burbidge, W. W. Noll
Journal: Journal of Clinical Oncology (2005)

9514 Background: Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is an autosomal dominant cancer syndrome that accounts for ∼5% of colorectal and endometrial cancers in the US. HNPCC is caused by mutations in one of several mismatch repair genes, with mutations in MLH1 and MSH2 accounting for >90% of cases. We compared the number of mutations in MLH1 and MSH2 detected by sequencing to the number detected by Southern blot (SB) analysis. Methods: DNA was extracted from consecutive blood samples submitted for MLH1 and MSH2 analysis by patients across the US. All exons and immediately adjacent intronic regions were sequenced by standard methods. Standard SB analysis was performed on three separate restriction enzyme digests and analyzed by three independent reviewers. Results: Of the first 288 samples analyzed, 30 (10%) were positive for a deleterious mutation by sequencing (20 MSH2, 10 MLH1) and 11 (4%) were positive for large deletions by SB analysis (8 MSH2, 3 MLH1), consistent with previously published papers. For the 75 patients with colorectal or endometrial cancer and 2 or more affected relatives, 14 (17%) were positive for a mutation by sequencing and 9 (12%) were positive for a large deletion. For the 76 affected patients with 1 or no affected relatives, 12 (16%) had a mutation by sequencing and 1 (1%) had a large deletion. For the 16 affected patients not providing a family history, 1 (6%) had a mutation by sequencing and 0 (0%) had a large deletion. The deletions were spread across both genes and ranged from single exons to the entire gene. Conclusions: Large rearrangement analysis of MLH1 and MSH2 substantially increases the detection rate of mutations in these genes and should be included in the genetic work-up of patients suspected of having HNPCC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Myriad Genetic Laboratories Myriad Genetic Laboratories
Central Nervous System Relapse In Adults With Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Amir Hamdi, Raya Mawad, Antonio Di Stasi, Roland Bassett, Roberto Ferro, Ron Ram, Gabriela Rondon, Richard E Champlin, Brenda M. Sandmaier, Kristine C. Doney, Merav Bar, Partow Kebriaei
Journal: Blood (2013)