tbuckley/cabot-search huggingface dataset:
Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel—Letter
Authors: María Apellániz-Ruiz, Lara Sánchez-Barroso, Gerardo Gutiérrez-Gutiérrez, María Sereno, Jesús García-Donás, Elisabeth Åvall-Lundqvist, Henrik Gréen, Kim Brøsen, Troels K. Bergmann, Cristina Rodríguez-Antona
Journal: Clinical Cancer Research (2015)

We have with great interest read the pharmacogenetic study by Abraham and colleagues ([1][1]) reporting SNPs associated with paclitaxel-induced neuropathy. The identification of markers predictive of sensory neuropathy is an important clinical problem for taxanes, vinca-alkaloids, platinum compounds
Abstract 17459: Donor Organ Specific Exosome Platform for Monitoring Transplant Organ Rejection in an in vivo Mouse Heterotopic Heart Transplant Model
Authors: Susan Rostami, Ming Hsu, Yanping Luo, Michael Acker, Ali Naji, Douglas Taylor, Prashanth Vallabhajosyula
Journal: Circulation (2013)

Introduction: In heart transplantation, there is a critical need for development of serum biomarkers to monitor for donor organ rejection/ injury, which remains a major cause of morbidity and morta...
A microarray approach to identify vorinostat-restored signaling pathways in leukemia cells.
Authors: M. Trus, Y. Lin
Journal: Journal of Clinical Oncology (2010)

e13634 Background: Acute myelogenous leukemia (AML) remains incurable for most patients and novel therapeutic approaches are needed. Genes are often epigenetically silenced in AML through the recruitment of histone deacetylases (HDACs). Agents that inhibit HDACs (HDACi) represent a novel treatment approach to AML, however, it would be of benefit to tailor therapies based on individual epigenetic profiles. In this study, we used a microarray approach to identify epigenetically silenced pathways in AML (OCI/AML-2) cells that could be restored by treatment with the HDACi vorinostat. Methods: OCI/AML-2 cells were treated with vorinostat 1μM or control conditions for 4 hours. Changes in gene expression were measured using Affymetrix Human Genome U133 Plus 2.0 arrays. Human Tiling 2.0R Array sets identified chromosomal regions with increased histone-acetylation after treatment by hybridizing probes generated from chromatin immunoprecipitated from OCI/AML-2 cells with anti-acetylated H3 and H4 histone antibodies. Results: After treatment with vorinostat, we identified 6,847 up-regulated and 1,925 down-regulated genes using expression arrays. Gene Set Enrichment Analyses (GSEA) grouped these genes into 362 up-regulated and 319 down-regulated gene sets controlling cellular growth, differentiation, and survival pathways. Tiling array experiments identified 4500 chromosomal regions with potentially increased levels of histone-acetylation after vorinostat-treatment. GSEA grouped these regions into 98 pathways that were up-regulated and 28 pathways that were down-regulated by vorinostat. Ingenuity pathway analyses identified the principle canonical pathways induced by vorinostat to be regulators of molecular cancer-signaling, gonadotropin release hormone signaling, and transforming growth factor beta signaling in the expression arrays and molecular cancer- signaling, Gα12/13 signaling, and p21 activated kinase signaling in the tiling arrays. Conclusions: Vorinostat is an effective regulator of gene expression in OCI/AML-2 cells. This microarray approach identifies specific epigenetic targets of vorinostat and represents a method that could lead to the development of tailored AML therapies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck
Attitudes and behaviors on physician-assisted death: a study of Michigan oncologists.
Authors: D J Doukas, D Waterhouse, D W Gorenflo, J Seid
Journal: Journal of Clinical Oncology (1995)

PURPOSE To ascertain the attitudes of oncologists toward physician-assisted death, ie, physician-assisted suicide and active euthanasia, as well as their experiences with these activities and their opinions toward their legalization. METHODS A survey was mailed to all practicing 250 oncologists in the state of Michigan, with subsequent development of psychometric scales and their correlation with self-reported behaviors in physician-assisted death. RESULTS Analysis revealed five distinct, meaningful factors regarding approval or disapproval of physician-assisted death. These factors reflected global attitudes toward physician-assisted death, passive euthanasia, philosophical prohibitions toward physician-assisted death, concerns of legal consequences with physician-assisted death, and attitudes that physician-assisted death could be avoided with better end-of-life care (alpha = .94, .74, .76, .87, and .84, respectively). High levels of therapy withdrawal were reported (81%), with significant reservations toward assisted suicide and active euthanasia, although reported participation in such actions was noteworthy (18% and 4%, respectively). The scales reflecting global and philosophical attitudes correlated with several attitudes and behaviors toward physician-assisted death (P &lt; .001). Legislation that would allow physician-assisted death was favored by 20.8% of respondents. CONCLUSION Although they have reservations about physician-assisted death, significant numbers of oncologists are willing to consider such actions should they become legal. Given the substantial number of physicians who report that they have already participated in physician-assisted death, these findings may help better understand the attitudes that motivate physician behaviors toward assisted death.
Abstract 3146: Reverse Cardiac Remodeling 2 Years After Marked Weight Loss From Gastric Bypass Surgery
Authors: Kimberly Morley, Nathaniel Hall, Ronny Jiji, Erick Avelar, Theophilus Owan, Nathan Segerson, Travis G Ault, Ted Adams, Steve Hunt, Sheldon E Litwin
Journal: Circulation (2007)
Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation.
Authors: D G Pfister, L B Harrison, E W Strong, J P Shah, R W Spiro, D H Kraus, J G Armstrong, M J Zelefsky, D E Fass, M H Weiss
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer. PATIENTS AND METHODS From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended. RESULTS With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet. CONCLUSION This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies.
Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery
Authors: Paula M De Angelis, Debbie H Svendsrud, Katherine L Kravik, Trond Stokke
Journal: Molecular Cancer (2006)

Abstract Background Treatment of cells with the anti-cancer drug 5-fluorouracil (5-FU) causes DNA damage, which in turn affects cell proliferation and survival. Two stable wild-type TP53 5-FU-resistant cell lines, ContinB and ContinD, generated from the HCT116 colon cancer cell line, demonstrate moderate and strong resistance to 5-FU, respectively, markedly-reduced levels of 5-FU-induced apoptosis, and alterations in expression levels of a number of key cell cycle- and apoptosis-regulatory genes as a result of resistance development. The aim of the present study was to determine potential differential responses to 8 and 24-hour 5-FU treatment in these resistant cell lines. We assessed levels of 5-FU uptake into DNA, cell cycle effects and apoptosis induction throughout treatment and recovery periods for each cell line, and alterations in expression levels of DNA damage response-, cell cycle- and apoptosis-regulatory genes in response to short-term drug exposure. Results 5-FU treatment for 24 hours resulted in S phase arrests, p53 accumulation, up-regulation of p53-target genes on DNA damage response ( ATF3 , GADD34 , GADD45A , PCNA ), cell cycle-regulatory ( CDKN1A ), and apoptosis-regulatory pathways ( FAS ), and apoptosis induction in the parental and resistant cell lines. Levels of 5-FU incorporation into DNA were similar for the cell lines. The pattern of cell cycle progression during recovery demonstrated consistently that the 5-FU-resistant cell lines had the smallest S phase fractions and the largest G 2 (/M) fractions. The strongly 5-FU-resistant ContinD cell line had the smallest S phase arrests, the lowest CDKN1A levels, and the lowest levels of 5-FU-induced apoptosis throughout the treatment and recovery periods, and the fastest recovery of exponential growth (10 days) compared to the other two cell lines. The moderately 5-FU-resistant ContinB cell line had comparatively lower apoptotic levels than the parental cells during treatment and recovery periods and a recovery time of 22 days. Mitotic activity ceased in response to drug treatment for all cell lines, consistent with down-regulation of mitosis-regulatory genes. Differential expression in response to 5-FU treatment was demonstrated for genes involved in regulation of nucleotide binding/metabolism ( ATAD2 , GNL2 , GNL3 , MATR3 ), amino acid metabolism ( AHCY , GSS , IVD , OAT ), cytoskeleton organization ( KRT7 , KRT8 , KRT19 , MAST1 ), transport ( MTCH1 , NCBP1 , SNAPAP , VPS52 ), and oxygen metabolism ( COX5A , COX7C ). Conclusion Our gene expression data suggest that altered regulation of nucleotide metabolism, amino acid metabolism, cytoskeleton organization, transport, and oxygen metabolism may underlie the differential resistance to 5-FU seen in these cell lines. The contributory roles to 5-FU resistance of some of the affected genes on these pathways will be assessed in future studies.
Agencies raise health concerns over treatment of Kos migrants
Authors: Adrian O’Dowd
Journal: BMJ (2015)

International aid organisations and charities have raised concern over the treatment, health, and living conditions of migrants, refugees, and asylum seekers on the Greek island of Kos.

The charity Medecins Sans Frontieres (MSF) said that more than 7000 people had arrived in Kos seeking help since July and that some had been held in an “ill equipped” sports stadium by the Greek authorities.

The mayor of Kos, Georgios Kyritsis, has said, however, that “fleeting and minor discord” had occurred during the process of helping the new arrivals and that the situation was now under control.

MSF said that in the absence of proper reception facilities many of the new arrivals had been directed to put up tents in public parks and squares in Kos town or were sleeping outside the police station, without access …
Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children
Authors: M. T. Salam, T. M. Bastain, E. B. Rappaport, T. Islam, K. Berhane, W. J. Gauderman, F. D. Gilliland
Journal: Allergy (2010)

To cite this article: Salam MT, Bastain TM, Rappaport EB, Islam T, Berhane K, Gauderman WJ, Gilliland FD. Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children. Allergy 2011; 66: 412–419. Abstract Background: Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. In the nitric oxide (NO) synthesis pathway, nitric oxide synthases (encoded by NOS1, NOS2A, and NOS3) and arginases (encoded by ARG1 and ARG2) compete for L-arginine. Although FeNO levels are higher in children with asthma/allergy, influence of these conditions on the relationships between variations in these genes and FeNO remains unknown. The aims of the study were to evaluate the role of genetic variations in nitric oxide synthases and arginases on FeNO in children and to assess the influence of asthma and respiratory allergy on these genetic associations. Methods: Among children (6–11 years) who participated in the southern California Children's Health Study, variations in these five genetic loci were characterized by tagSNPs. FeNO was measured in two consecutive years (N = 2298 and 2515 in Years 1 and 2, respectively). Repeated measures analysis of variance was used to evaluate the associations between these genetic variants and FeNO. Results: Sequence variations in the NOS2A and ARG2 loci were globally associated with FeNO (P = 0.0002 and 0.01, respectively). The ARG2 association was tagged by intronic variant rs3742879 with stronger association with FeNO in asthmatic children (P-interaction = 0.01). The association of a NOS2A promoter haplotype with FeNO varied significantly by rs3742879 genotypes and by asthma. Conclusion: Variants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings.
Attitudes and Perceptions About Smoking Cessation in the Context of Lung Cancer Screening
Authors: Steven B. Zeliadt, Jaimee L. Heffner, George Sayre, Deborah E. Klein, Carol Simons, Jennifer Williams, Lynn F. Reinke, David H. Au
Journal: JAMA Internal Medicine (2015)

Broad adoption of lung cancer screening may inadvertently lead to negative population health outcomes if it is perceived as a substitute for smoking cessation.To understand views on smoking cessation from current smokers in the context of being offered lung cancer screening as a routine service in primary care.As an ancillary study to the launch of a lung cancer screening program at 7 sites in the Veterans Health Administration, 45 in-depth semi-structured qualitative interviews about health beliefs related to smoking and lung cancer screening were administered from May 29 to September 22, 2014, by telephone to 37 current smokers offered lung cancer screening by their primary care physician. Analysis was conducted from June 15, 2014, to March 29, 2015.Attitudes and perceptions about the importance of smoking cessation in the context of lung cancer screening.Lung cancer screening prompted most current smokers to reflect for the first time on what smoking means for their current and future health. However, 17 of 35 (49%) participants described mechanisms whereby screening lowered their motivation for cessation, including the perception that undergoing an imaging test yields the same health benefits as smoking cessation. Other misperceptions include the belief that everyone who participates in screening will benefit; the belief that screening and being able to return for additional screening offers protection from lung cancer; the perception by some individuals that findings from screenings have saved their lives by catching their cancer early when indeterminate findings are identified that can be monitored rather than immediately treated; and a reinforced belief in some individuals that a cancer-free screening test result indicates that they are among the lucky ones who will avoid the harms of smoking.In this qualitative, lung cancer screening prompted many current smokers to reflect on their health and may serve as a potential opportunity to engage patients in discussions about smoking cessation. However, several concerning pathways were identified in which screening, when offered as part of routine care and described as having proven efficacy, may negatively influence smoking cessation. Health care professionals should be aware that the opportunity for early detection of lung cancer may be interpreted as a way of avoiding the harms of smoking. To promote cessation, discussions should focus on the emotional response to screening rather than clinical details (eg, nodule size) and address misperceptions about the value of early detection so that screening does not lower motivation to quit smoking.
Matched-Pair Analysis of Conformal High–Dose-Rate Brachytherapy Boost Versus External-Beam Radiation Therapy Alone for Locally Advanced Prostate Cancer
Authors: Larry L. Kestin, Alvaro A. Martinez, Jannifer S. Stromberg, Gregory K. Edmundson, Gary S. Gustafson, Donald S. Brabbins, Peter Y. Chen, Frank A. Vicini
Journal: Journal of Clinical Oncology (2000)

We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR).From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone.EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001).Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.
Abstract 2556: The predictive role of tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery
Authors: Po-Hao Feng, Chih-Teng Yu, Chin-Yang Wu, Tzung-Hai Yen, Kang-Yun Lee
Journal: Cancer Research (2014)

Abstract Introduction: Neoadjuvant chemotherapy improves survival in patients with pN2 stage IIIA non-small cell lung cancer (NSCLC). However, the majority relapse eventually even with mediastinal downstaging. Our study investigated the predictive role of tumor-associate macrophages (TAMs) in these patients. Methods: Between 2005 and 2008, twenty-two pN2 stage IIIA NSCLC patients underwent cisplatin/docetaxel neoadjuvant chemotherapy and surgery were retrospectively enrolled. Immunohistochemical staining of CD68 was used to identify macrophages in stored tissues. Results: The objective response rate was 68%, overall median disease-free survival (DFS) was 13.1 months (95% CI 6.1-20.2 months) and median overall survival (OS) 48.0 months (95% CI 24.0-72.1 months). Multiple Cox regression analysis showed mediastinal downstaging to pN0 (HR=0.039, 95% CI 0.004-0.349, p=0.004) and high total macrophage numbers (HR=1.01, 95% CI 1.002-1.017, p=0.012) were independent factors for DFS. In the 16 patients downstaged to pN0, those with low total macrophage numbers had longer DFS (median 33.4 months), compared with those with high numbers (13.4 months, p=0.037). Conclusions: Low total macrophage numbers were also an independent factor for better DFS in pN2 stage IIIA NSCLC patients receiving neoadjuvant chemotherapy and surgical resection, which association was kept in patients downstaged to pN0. Further prospective study is warranted to confirm the predictive role of TAM in these patients. Citation Format: Po-Hao Feng, Chih-Teng Yu, Chin-Yang Wu, Tzung-Hai Yen, Kang-Yun Lee. The predictive role of tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery. [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 2556. doi:10.1158/1538-7445.AM2014-2556
Abstract 9515: NMR Spectroscopy Uncovers Important Atherogenic Lipoprotein Abnormalities in Nonalcoholic Fatty Liver Disease: The Insulin Resistance Atherosclerosis Study (IRAS).
Authors: Steven M Haffner, Lynne E Wagenknecht, Carlos Lorenzo
Journal: Circulation (2011)

Introduction: Nonalcoholic fatty liver disease may be the most frequent cause of chronically elevated transaminase levels in the general population. One of these inexpensive and routinely measured enzymes, alanine aminotransferase (ALT) is an independent predictor of future cardiovascular disease and diabetes. ALT has been associated with dyslipidemia, but the extent of this relationship is not well described. Hypothesis: Because to its advantage over conventional methods, we hypothesized that proton nuclear magnetic resonance (NMR) spectroscopy could be better for detecting atherogenic lipoprotein abnormalities in nonalcoholic fatty liver disease. Thus, we analyzed the relation of ALT to lipoproteins measured by NMR spectroscopy and conventional methods in non-diabetic participants in the IRAS. Methods: Cross-sectional analysis of lipoproteins and apolipoproteins in 912 non-diabetic participants in the IRAS. In fasting single fresh plasma samples, we measured plasma lipoproteins by conventional methods and NMR spectroscopy and apolipoprotein B (apo B) by immunoprecipitation. Insulin sensitivity was measured by the frequently sampled intravenous glucose tolerance test. Results: After adjusting for age, sex, race/ethnicity, and clinic, ALT was associated with triglycerides, LDL and HDL cholesterol, and apo B ( Table ). ALT had significant relationships with large VLDL, total LDL, IDL, small LDL, and large HDL particle concentrations plus VLDL, LDL, and HDL particle sizes. ALT remained associated with total LDL, IDL, and small LDL particle concentrations, LDL particle size, and apo B after the additional adjustment for waist circumference and insulin sensitivity. Conclusions: NMR spectroscopy uncovers a more extensive relationship between atherogenic lipoprotein abnormalities and ALT in non-diabetic individuals. These abnormalities could partially explain the relation of ALT to future cardiovascular disease.