tbuckley/cabot-search huggingface dataset:
Disseminated Rhabdomyosarcomas Formed in Kittens by Cultured Human Rhabdomyosarcoma Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R M McAllister, W A Nelson-Rees, E Y Johnson, R W Rongey, M B Gardner
Journal: JNCI Journal of the National Cancer Institute (1971)

Cultured human rhabdomyosarcoma cells (RD cell, line #2) were inoculated into the fetuses of 3 pregnant cats at approximately 40 days' gestation. Three of five surviving kittens from two litters developed disseminated rhabdomyosarcomas 46, 55, and 60 days after birth, respectively. One full-grown stillborn kitten of the third cat' had rhabdomyosarcomas in the liver and thymus. The tumors in all kittens looked like the original rhabdomyosarcoma from which the RD cell line was derived. Cell lines derived by tumor cell isolation from 3 cat tumors consisted of 2 cytologic types resembling those of the original tumor—polygonal cells and strap cells. Metaphases of these cells contained many aberrations, but the chromosome pattern was like that of the original human rhabdomyosarcoma cells. Those lines tested had a rapid generation time, a high saturation density, formed colonies in agar, and contained myoglobin. One cell line was inoculated into fetal cats, and rhabdomyosarcomas composed of human cells formed in 2 of 3 surviving kittens at 43 and 47 days after birth, respectively. Although the parent RD cell line contained no detectable C-type virus particles, 2 cat tumors and 1 cell line derived from 1 of these tumors contained C-type virus particles of unknown origin.
Comparison between epidermal growth factor receptor (EGFR) gene in primary non-small cell lung cancer (NSCLC) and in fine needle aspirates from metastatic sites
Authors: C. Bozzetti, M. Tiseo, C. Lagrasta, R. Nizzoli, F. Leonardi, D. Gasparro, E. Spiritelli, V. Franciosi, G. Rindi, A. Ardizzoni
Journal: Journal of Clinical Oncology (2007)

21081 Background: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently proposed to predict which non-small cell lung cancer patients (NSCLC) are expected to benefit from EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared to primary NSCLC. In all studies, FISH have been performed on histological material. The possibility to perform FISH analysis on cytological material obtained by fine-needle aspiration from superficial and deep metastases would allow to know the real EGFR status when the metastatic site is not accessible for biopsy. Methods: EGFR gene copy number was analyzed by FISH on fine-needle aspirates (FNAs) obtained from 18 patients with metastatic NSCLC (11 lymphnod, 2 liver, 1 abdomen, 2 skin, 2 pleural effusion) and results were compared with those obtained on corresponding paraffin histological sections from the primary tumor. Results: The feasibility of EGFR-FISH on cytology was 89%; 2/18 samples were not evaluable because of lack of hybridization. EGFR-FISH was positive (= 4 EGFR copy number; Cappuzzo F. et al, JNCI 2005) in 69% (11/16) of the metastases and in 38% (6/16) of the primary tumors. Five of the 16 cases were EGFR positive on both primary tumor and metastatic site and 4 were negative on both primary tumor and metastasis. Seven cases (44%) showed primary tumor vs. metastasis discordance: in 6 cases EGFR was positive in the metastatic site but not in the primary tumor, while in one sample EGFR was positive in the primary tumor but not in the metastasis. Conclusions: EGFR-FISH can be reliably assessed on FNAs obtained from NSCLC metastases. Possible changes in EGFR status during the metastatic progression as well as cancer heterogeneity may account for discrepancies observed between primary tumor and metastatic sites. These findings should be considered in future studies which will be design to better elucidate the predictive role of EGFR-FISH in NSCLC. No significant financial relationships to disclose.
Lung mechanics in obesity and changes with bariatric surgery: The role of airway smooth muscle tone and airway unloading
Authors: Ubong Peters, Swati Bhatawadekar, Gail Dechman, James Ellsmere, Paul Hernandez, Dietrich Henzler, Geoffrey Maksym
Journal: European Respiratory Journal (2013)

Introduction:  Obesity reduces airway caliber by unloading the airway wall often resulting in sleep disordered breathing and asthma-like symptoms. These respiratory conditions often improve following weight loss however the mechanisms are not well understood.  Methods:  We investigated the role of unloading the airway smooth muscle in 8 obese patients and the change in lung mechanics before and 5 weeks after bariatric surgery by measuring respiratory system resistance ( Rrs ) and reactance ( Xrs ) with the forced oscillation technique (TremoFlo TM ) at 6, 11, 19 Hz in the upright and supine position, and pre- and post-bronchodilation (BD, 200 mcg salbutamol).  Results and Discussion:  Before surgery and pre-BD, the change from upright to supine increased average  Rrs  from 3.61±0.6 to 4.19±0.54 cm H 2 0 l -1 s -1  (p Xrs  decreased at each frequency (by 1.01±0.28 cm H 2 0 l -1 s -1  at 11 Hz). These differences disappeared following a mean weight loss of 11.3±0.7 kg after surgery. Although posture had no effect on  Rrs  post-BD, it caused a decrease in  Xrs  both before and after surgery. Similarly, BD in the upright posture caused pre-surgery  Xrs  at 6 Hz to increase by 0.8±0.33 cm H 2 0 l -1 s -1  but no effect post-surgery while BD in the supine posture decreased average  Rrs  by 20±9% before surgery but not after.  Conclusion:  The reductions in supine induced changes in  Rrs  and  Xrs  following surgery suggest a decrease in unloading of the airway wall from upright to supine due to weight loss. This is consistent with the loss of the supine BD effect on  Rrs  and  Xrs  post-surgery which also implies an increase in peripheral airway baseline diameter and improved lung function.
HSP60 activity on 16HBE cells after oxidative and pro-inflammatory stimuli
Authors: Davide Vallese, Alessandro Pitruzzella, Isabella Gnemmi, Fabio Bucchieri, Francesco Cappello, Bruno Balbi, Alberto J.L. Macario, Everly Conway de Macario, Antonino Di Stefano
Journal: European Respiratory Journal (2014)

Background: We reported increased HSP60 in bronchial epithelium of COPD patients. HSP60 can bind Toll-like receptors but the subsequent cellular response is not yet understood.  Aim: To evaluate the response of bronchial epithelial cells to HSP60 alone or in combination with oxidative and pro-inflammatory stimuli.  Methods: Human bronchial epithelial cells (16HBE) were cultured for 1, 2, 4, 8, and 24h in the absence or presence of LPS (10 µg/mL), H 2 O 2  (100µM), Citomix (IL-1s 1 ng/mL, TNFα 10 ng/mL and IFN-γ 10 ng/mL) and low-endotoxin HSP60 (1 µg/mL), each alone or in combination with another. Measurement of effects was by qRT-PCR; mRNA normalized with GAPDH.  Results: Exposure of 16HBE to oxidative stress (H 2 O 2 ) up-regulated IL-8 mRNA at 2 h (non treated vs treated, mean±SD: 0.72±0.011 vs 0.85±0.007 ΔCt; p=0.0209). Conversely, the combination HSP60 + H 2 O 2  inhibited IL-8 mRNA up-regulation at 2 h (0.82±0.009 vs 0.81±0.031 ΔCt; p=0.2482). LPS caused up-regulation of IL-8 mRNA after 2 h and 4 h (0.81±0.019 vs 0.85±0.020 ΔCt; p=0.0209; 0.77±0.013 vs 0.81±0.030 ΔCt; p=0.0344, respectively). LPS + HSP60 evidenced protection only after 4 h of exposure (0.77±0.039 vs 0.75±0.025 ΔCt; p=0.2482).  Conclusion: Partial protection by HSP60 was found against the pro-inflammatory activity of oxidative stress and LPS in 16HBE cells.
Novel technologies and emerging biomarkers for personalized cancer immunotherapy
Authors: Jianda Yuan, Priti S. Hegde, Raphael Clynes, Periklis G. Foukas, Alexandre Harari, Thomas O. Kleen, Pia Kvistborg, Cristina Maccalli, Holden T. Maecker, David B. Page, Harlan Robins, Wenru Song, Edward C. Stack, Ena Wang, Theresa L. Whiteside, Yingdong Zhao, Heinz Zwierzina, Lisa H. Butterfield, Bernard A. Fox
Journal: Journal for ImmunoTherapy of Cancer (2016)

The culmination of over a century's work to understand the role of the immune system in tumor control has led to the recent advances in cancer immunotherapies that have resulted in durable clinical responses in patients with a variety of malignancies. Cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the therapeutic landscape for cancer patients. However, despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Thus, there is a growing need to identify predictive and prognostic biomarkers that enhance our understanding of the mechanisms underlying the complex interactions between the immune system and cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) reconvened an Immune Biomarkers Task&nbsp;Force to review state of the art technologies, identify current hurdlers, and make recommendations for the field. As a product of this task&nbsp;force, Working Group 2 (WG2), consisting of international experts from academia and industry, assembled to identify and discuss promising technologies for biomarker discovery and validation. Thus, this WG2 consensus paper will focus on the current status of emerging biomarkers for immune checkpoint blockade therapy and discuss novel technologies as well as high dimensional data analysis platforms that will be pivotal for future biomarker research. In addition, this paper will include a brief overview of the current challenges with recommendations for future biomarker discovery.
Abstract 19826: Cardiac DGAT1 Deficiency Decreases Triglyceride Turnover and Alters Substrate Utilization
Authors: Nathan Roe, Rong Tian
Journal: Circulation (2014)

Triglyceride (TG) metabolism in the heart has been suggested to regulate PPARα activity and fatty acid oxidation. Reduced TG content and turnover has also been shown in rodent models of heart failure. We found that patients with heart failure displayed decreased mRNA levels of diacylglycerol:acyltransferase 1 (DGAT1), the rate limiting enzyme in TG synthesis (0.56±0.06 fold of NF, p=0.0001) and a lower myocardial TG content (3.65±0.41 vs. 8.27±1.48 mg/g tissue in NF, n=8-11, p=0.019). Therefore we hypothesized reduced TG synthesis caused metabolic remodeling in heart failure. In mice with tamoxifen-inducible cardiac specific deletion of DGAT1 (iKO) TG turnover was reduced. 13 C NMR spectroscopy in perfused hearts revealed a 30% reduction in incorporation of labeled fatty acids (FA) into TG in iKO (40 minute peak area 7.86±0.26 vs. 5.73±0.50) with no changes in total TG content. To test whether these changes affect myocardial energetics and contractile function, we simultaneously measured high energy phosphate content and contractile function using 31 P NMR in isolated perfused hearts. Contractile function and PCr/ATP ratio was unchanged in iKO hearts perfused with FA, lactate and glucose. Furthermore, there is no difference between genotypes in the expression of PPARα or its downstream target genes at baseline or after 5 weeks of high fat diet, indicating that TG turnover has minimal effect on PPARα activity. However, iKO hearts showed increased oxidation of exogenous fatty acid (67.0±4.1% vs. 48.5±5.3%) and reduced glucose oxidation (12.9±4.2% vs. 27.4±4.5%, n=5-7). These observations suggest that reduced TG synthesis diverts exogenous FA from the TG pool towards oxidative metabolism. To evaluate the dependence of iKO hearts upon exogenous FA, hearts were perfused with glucose as the only substrate. The ability to utilize TG was reduced in iKO resulting in a 50% higher TG content after 20 min perfusion, which was associated with a reduced left ventricular developed pressure (119±6 vs. 97±7 mmHg for control and iKO respectively). Taken together, we found that DGAT1 deficiency in the heart reduced TG turnover and increased reliance on the oxidation of exogenous FA, a phenotype that may contribute to the lack of metabolic flexibility in heart failure.
Morphological Investigation of Human Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J A Sykes, L Recher, P H Jernstrom, J Whitescarver
Journal: JNCI Journal of the National Cancer Institute (1968)

Twenty-two human breast cancers and two benign breast tumors were studied in the electron microscope. Human breast tumors were found to retain certain characteristics of their tissue of origin. There was some ductal differentiation in all these tumors. Unlike normal epithelial cells of the mammary gland, tumor cells frequently showed intracytoplasmic ductules and numerous cytoplasmic microfibrils identified as tonofibrils. These two cytological features were considered pathognomonic for cancer cells. The significance and nature of the nuclear “inclusions” and of some cytoplasmic structures described are unknown. No structures resembling any known infectious or oncogenic viruses were observed in the human breast material examined.
Abstract 5: Neovascularization By Substance-p- Mobilized Epc And Msc In Vitro And In Vivo
Authors: Hyun Sook Hong, Suna Kim, Youngsook Son
Journal: Circulation Research (2014)

Bone marrow stem cells, especially, endothelial precursor cells (EPC), mesenchymal stem cells (MSC) or hematopoietic stem cell (HSC) are expected as reparative cells for the repair of a variety of tissue damages such as stroke and myocardial infarction, even though their role in the repair is not demonstrated. This report was investigated to find a role of Substance-p (SP) as a reparative agent in the tissue repair requiring EPC and MSC. In order to examine EPC (EPC SP ) and MSC (MSC SP ) mobilized by SP, we injected SP intravenously for consecutive 2 days and saline was injected as a vehicle. At 3 post injection, peripheral blood (PB) was collected.To get mesenchymal stem cells or endothelial progenitor cells, MNCs were incubated in MSCGM or EGM-2 respectively for 10 days. Functional characteristics of the EPC SP were proven by the capacity to form endothelial tubule network in the matrigel in vitro and in the matrigel plug assay in vivo. In contrast, MSC SP did not form a tube-like structure but formed a pellet-structure on matrigel. However, when both cells were premixed before the matrigel assay, much longer and branched tubular network was formed, in which a-SMA expressing MSC SP were decorating outside of the endothelial tube, especially enriched at the bifurcating point. MSC SP may contribute and reinforce elaborate vascular network formation in vivo by working as pericyte-like cells. Thus, the EPC SP and MSC SP were labeled with PKH green and PKH red respectively and their tubular network was examined. Well organized tubular network was formed, which was covered by PKH green labeled cells and was decorated in a punctate pattern by PKH red labeled cells. In order to investigate the role of EPC SP and MSC SP specifically in vivo, rabbit EPC SP and MSC SP were transplanted to full thickness skin wound. The vessel of EPC SP -transplanted groups was UEA-lectin+, which was not covered with a-SMA+ pericytes but EPC SP + MSC SP -transplanted groups showed, in part, a-SMA+ pericyte-encircled UEA-lectin+ vessels. This proved the specific role of MSC SP as pericytes. From these data, we have postulated that the collaboration of MSC and EPC is essential for normal vessel structure and furthermore, accelerated wound healing as ischemia diseases, which can be stimulated through by SP injection.
Does NSCLC patient-rated performance status predict survival more accurately than physician ratings?
Authors: E. Dajczman, G. Kasymjanova, N. Swinton, D. St-Pierre, T. Swanson, H. Kreisman, J. S. Agulnik, V. Cohen, N. MacDonald, D. Small
Journal: Journal of Clinical Oncology (2007)

9022 Background: The Eastern Cooperative Oncology Group (ECOG) score is a well known predictor of survival, which impacts on treatment decisions. Patient (pt) rated activity level, using the Patient Generated Subjective Global Assessment (PG-SGA) scale, is identical in criteria to the ECOG scale used by physicians. We compared the patient rated activity level (Pt-PS) to physician rated PS (MD-PS), at baseline, and evaluated survival with respect to the 2 PS ratings. Methods: Pts with newly diagnosed advanced NSCLC (stages 3–4) completed a PG-SGA self rated questionnaire, which was then compared to the physician-generated ECOG score recorded prior to any treatment using a Wilcoxon signed rank test. Pts were treated with standard chemotherapy. Survival analysis was performed using a Kaplan Meier analysis and Cox regression. Results: 92 pts (M: F-48:44) with a mean age of 65 years (39–83) were included. 67 (73%) presented with stage 4 disease. 62 (67%) had an MD-PS of 0–1, whereas only 51 (55%) had a Pt-PS of 0 -1. MD-PS 3–4 was seen in 9 (10%), compared to 28 (30%) by Pt-PS. Pt-PS was significantly different from MD-PS in 48% of scores (p=0.003). When scores were not congruent, 29/44 (66%) pts evaluated themselves as having a worse PS than the physician. Survival analysis demonstrated that stage and functional status irrespective of method of reporting was predictive of survival (p=0.01 for MD-PS and p=0.001 for Pt-PS). However, when comparing median survival by method of performance status evaluation, Pt-PS was associated with superior stratification of survival than MD-PS ( table 1 ). Conclusions: Pt-PS and MD-PS are not congruent almost 50% of the time. Pt-PS allows for better stratification of survival and should be further evaluated in prospective trials. No significant financial relationships to disclose. [Table: see text]
Abstract 10622: Impact of Acute Coronary Syndrome on Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention
Authors: Ji-Hwan Kim, Seung-Hyuk Choi, Jeong Hoon Yang, Ki Hong Choi, Sehyo Yune, Young Bin Song, Joo-yong Hahn, Jin-Ho Choi, Hyeon-Cheol Gwon
Journal: Circulation (2013)

Background:  Patients who undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) have poor prognosis than stable coronary artery disease (CAD). Few studies to compare the impact of ACS between patients without chronic kidney disease (CKD) and with CKD are present. The aim of this study was to compare the long-term clinical events after percutaneous coronary intervention (PCI) between patients with ACS and with stable CAD according to the presence of CKD.   Methods:  We enrolled consecutive 5963 patients who had undergone PCI and retrospectively collected clinical, laboratory and angiographic data. CKD was defined as eGFR  2 . The primary endpoint was the major adverse cardiac events (MACE: cardiac death, myocardial infarction or target lesion revascularization).   Results:  Among 5963 patients, 879 (14.7%) had CKD and 5084 (85.3%) had preserved kidney function. The MACE rate was higher in CKD patients than Non-CKD patients during a median follow-up of 48 months (22.3% vs. 10.0%, p   Conclusion:  ACS is associated with higher incidence of cardiovascular events than stable CAD after coronary revascularization. In CKD patients, the adverse effect of ACS on cardiovascular outcomes is augmented.
Environments organize the verbal brain
Authors: A. Charles Catania
Journal: Behavioral and Brain Sciences (2014)

Abstract FOXP2 expression in the evolution of language derives from its role in allowing vocal articulation that is sensitive to its consequences. The discrete verbal discourse it allows must have evolved recently relative to affective features of vocal behavior such as tone of voice. Because all organ systems must have evolved in the service of behavior, attention is given to ways in which environments may have driven brain organization.
Cancer clinical trials (CCT) awareness and attitudes in cancer survivors (Ca surv)
Authors: R. L. Comis, D. Colaizzi, J. D. Miller
Journal: Journal of Clinical Oncology (2006)

6061 Background: A web-based survey of attitudes and awareness of Ca surv towards CCT was performed from 3–4, 2005. The survey instrument was developed jointly by the Coalition of Cancer Cooperative Groups (CCCG) and Northwestern Univ (NU) and executed by NU and Knowledge Networks (KN). Methods: Ca surv were obtained from a panel of 40,000 adults through KN, based on a US households national probability sample who agree to weekly surveys in exchange for a free WebTV box and ISP service. 2,029 panel members reported a cancer diagnosis. 1,788/2,029 (88%) agreed to participate. Results: Ten-percent of Ca surv were aware that CCT participation was an option. In 73%, a physician was the source of the CCT awareness. Awareness was related to time since diagnosis (&lt; 9 yrs vs &gt; 9yrs); gender (females &gt; males); age (younger &gt; older), and education (baccalaureate vs less). Awareness varied according to cancer type: leukemia, 26%; breast, 15%; lymphoma and lung, 14%; prostate, 12%; melanoma and renal cell, 10%; colorectal and bladder; 6–3%. Awareness was dependent (p &lt; .01) on type of treatment: surgery 5% (n, 880); surgery and RT, 7% (n, 181); RT, 10% (n, 107); chemotherapy, 18% (n, 488). Of the last group, 44% enrolled into CCT; 33% declined and 11% were either ineligible or not offered a CCT. Those who declined were concerned that the new approach might be “less effective” (40%) and about “randomization” (18%). CCT Ca surv reported a high level of satisfaction on a 0 (worst) to 10 (best) scale: “treated with dignity and respect”, 9.6; “overall very positive experience”, 9.3; “recommend to a family member or friend”, 8.8. Conversely, the response to “I felt like a guinea pig” was 1.7. Conclusions: In summary, assessing issues such as awareness, participation and accrual onto CCT must adjust for key demographic, disease and treatment related factors. The CCT experience is valued and appreciated by Ca surv as they move the field forward. No significant financial relationships to disclose.
Abstract 11878: Forty-Year Change in Coronary Heart Disease Mortality Among Working Aged Men and Women in Eastern Finland: The Role of Primary Prevention and Risk Factor Reduction
Authors: Pekka Jousilahti, Tiina Laatikainen, Markku Peltonen, Katja Borodulin, Satu Männistö, Antti Jula, Veikko Salomaa, Pekka Puska, Erkki Vartiainen
Journal: Circulation (2014)

Introduction:  In the late 1960s, Eastern Finland had the highest CHD mortality in the world. Community-based CVD prevention program - the North Karelia Project - was launched in 1972. This study aims to estimate the extent to which changes in the main CVD risk factors explain the decline in CHD mortality among working aged population in Eastern Finland.   Methods:  Predicted change in CHD mortality was estimated by a logistic regression model using risk factor data of 37,177 men and women aged 30-59 years who participated in CVD risk factor surveys conducted every five years since 1972. The latest FINRISK survey was done in 2012. Data on observed CHD mortality were obtained from the National Causes of Death Register. The register includes all deaths among Finnish citizens and the data is practically complete.   Results:  From early seventies (1969-1972) to 2012 CHD mortality decreased among men aged 35 to 64 years by 82% (from 643 to 118 per 100,000). Among women the decrease was 84% (from 114 to 17 per 100,000). During the same time period, the levels of major CVD risk factors, smoking prevalence, serum total cholesterol and blood pressure decline remarkably, except a small increase in serum cholesterol and diastolic blood pressure levels between 2007 and 2012. During the first ten years, changes in major risk factors explained nearly all of the observed mortality reduction (table). Since mid-1980s, observed reduction in mortality has been larger than predicted. In the last ten years about two thirds of the CHD mortality reduction was explained by changes in classical risk factors and one third by other factors, including secondary prevention and treatment of acute CHD events.   Conclusion:  Population based primary prevention and reduction in the levels of major risk factors are crucial in lowering of disease burden and mortality due to CHD. An additional gain can be achieved by secondary prevention among high risk individuals and by treatment of acute events.