tbuckley/cabot-search huggingface dataset:
Abstract 1305: A comprehensive investigation of immune infiltrates in hepatocellular carcinoma
Authors: Sangho Yoon
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC), a major form of primary liver cancer, is one of the leading causes of cancer-related death, and is caused by a myriad of risk factors from chronic inflammation by viral infection to genetic defects. Recent investigations shed light on the importance and role of immune cells in tumor microenvironment; however, since a majority of studies have focused only on tumor sites, the role of immune cells in tumor-surrounding (or precancerous) area with chronic inflammation was not investigated in HCC in detail. For the treatment of HCC patients, liver transplant (total hepatectomy) has been reported to offer much longer survival and better outcome compared to patients who had local tumor resection (partial hepatectomy). Nonetheless, the significance of tumor-infiltrating immune cells (TICs) established in patients who had suffered from chronic inflammation is still vague. Here, we collected total 122 Korean HCC samples, followed by high-throughput RNA sequencing (RNA-seq), from various premalignant stages—fibrosis and dysplastic nodules, tumors to noncacerous normal liver tissues—enhanced with public RNA-seq datasets including HCC from TCGA. Decomposing immune cell types using the RNA-seq data revealed that TICs are dynamically changed with showing no or weak correlations in the normal liver tissues, while being intertwined into dense and strong correlation networks as the disease progresses. Intriguingly, patients who had total hepatectomy showed different composition of immune cells and longer disease-free survival compared to the partial hepatectomy group; however, the presence of regulatory T cells (Tregs) before the transplantation dampened this outcome in the total hepatectomy patients. Tregs in the total hepatectomy group were found to be specific to tumor sites, and were enriched upon tumor progression, while pretreatment, such as embolization, increased the presence of Tregs. Besides the specific immune cells in tumor sites, the composition of certain types of immune cells in tumor-surrounding inflamed tissues was also important for predicting patients' outcomes in HCC. Particularly, alternatively activated macrophages (M2-type) have more predictive power in the patients' outcome when they were inferred from the tumor-surrounding inflamed samples. Our study not only provides a dynamic map of tumor-surrounding and -infiltrating immune cells, but also offers understanding about immune cell networks in the progression of HCC. Citation Format: Sangho Yoon. A comprehensive investigation of immune infiltrates in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1305.
Abstract 4254: Associations of sleep, quality of life and energy level with breast cancer mortality and recurrence: The Shanghai Breast Cancer Survival Study
Authors: Jingjing Zhu, Pingping Bao, Hui Cai, Liang Shi, Ying Zheng, Wei Zheng, Xiao-ou Shu
Journal: Cancer Research (2018)

Abstract Background: Sleep disorder is highly prevalent among breast cancer patients. Whether sleep disorder is associated with breast cancer prognosis has rarely been investigated. The objective of this study is to prospectively assess the association of self-reported sleep difficulty and sleep quality with total mortality and breast-cancer specific mortality/recurrence in the Shanghai Breast Cancer Survival Study. Methods: This study included 4,219 women with stage I-III breast cancer diagnosed at an age between 20 to 75 years. Information on sleep attributes was collected at approximately 18 months and 36 months after breast cancer diagnosis. Information on disease recurrence and survival status was obtained via in-person follow-up and via record linkage with vital statistics registry data. Cox proportional hazard model was used to derive hazard ratios (HR) and confidence intervals (CIs) for all-cause mortality and breast cancer-specific mortality/recurrence. Stratified analyses according to self-reported overall quality of life, depression and energy level assessed at 18 months were also conducted. Results: During a median follow-up of 9.8 years (range: 0.1-12.2 years), 757 deaths due to any causes and 672 breast cancer recurrences or related deaths were recorded after the 18-month post-diagnosis survey. Sleep difficulty and low sleep quality were not significantly associated with total or breast-cancer specific mortality/recurrence. The respective HRs were 0.98 (95% CI: 0.79, 1.22) and 1.01 (95% CI: 0.77, 1.31) for total mortality and 1.04 (95% CI: 0.82, 1.31) and 0.93 (95% CI: 0.69, 1.26) for breast cancer-specific mortality/recurrence. On the other hand, low quality of life, depression and low energy level were significantly associated with increased total mortality, with HRs of 3.19 (2.45, 4.15), 1.61 (1.21, 2.14) and 1.53 (1.23, 1.91), respectively. These three factors did not modify the association of sleep measurements with breast cancer outcomes (all P-interactions &amp;gt; 0.10). Conclusions: In a large population-based cohort study, we did not observe any significant association of sleep difficulty and poor sleep quality with increased risk of death and recurrence in breast cancer patients. Instead, low quality of life and energy level were found to be associated with disease prognosis and thus they could be important indicators for targeting population with poor breast cancer prognosis. Citation Format: Jingjing Zhu, Pingping Bao, Hui Cai, Liang Shi, Ying Zheng, Wei Zheng, Xiao-ou Shu. Associations of sleep, quality of life and energy level with breast cancer mortality and recurrence: The Shanghai Breast Cancer Survival Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4254.
Abstract P126: Influence of CIMT as a Motivator for Health Behavior Change in a Heart Health Program
Authors: ElaineWalizer, MarinaVernalis, RandolphModlin
Journal: Circulation (2014)

Introduction: Carotid intima media thickness (CIMT) ultrasound is a known surrogate marker of atherosclerosis but few studies examine its influence on patient behavior. Motivation and self-efficacy (SE) are known predictors of health behavior change. This randomized, double-blind trial examined 1) use of CIMT images plus associated CVD risk to motivate adherence, and 2) the predictive ability of motivation and SE on adherence change. Methods: Patients with ≥ 2 cardiovascular disease (CVD) risk factors and subclinical atherosclerosis were assigned to either the intervention group [receive results weekly (R-CIMT)] or control group [withhold results (W-CIMT)]. All patients received a 12-week lifestyle program (Mediterranean diet, aerobic exercise, group support). Overall change in adherence from baseline to week 12 was determined using an ANCOVA model where % adherence was a composite measure of diet and exercise adherence. Initial motivation plus exercise and nutrition SE were assessed to determine their pr...
Abstract 3831: Development of near-infrared photoimmunotherapy targeting GD2-positive neuroblastoma
Authors: Hiroshi Nouso, Hiroshi Tazawa, Terutaka Tanimoto, Morimichi Tani, Takanori Oyama, Hiroaki Sato, Kazuhiro Noma, Shunsuke Kagawa, Hisataka Kobayashi, Takuo Noda, Toshiyoshi Fujiwara
Journal: Cancer Research (2018)

Abstract Background: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Despite the recent advances in the treatment of NB, patients with high-risk NB still have poor prognosis. Immunotherapy using anti-GD2 monoclonal antibody (mAb), which binds to disialoganglioside GD2 on the surface of NB cells, has recently become a standard treatment for high-risk NB. However, the therapeutic efficacy of anti-GD2 mAb is insufficient in many clinical trials. Therefore, the enhancement of therapeutic potential of anti-GD2 mAb is needed to improve the clinical outcome of patients with high-risk NB. Near-infrared photoimmunotherapy (NIR-PIT) is a promising antitumor strategy to enhance the therapeutic potential of immunotherapy using an antibody-photoabsorber conjugate (APC). In this study, we investigated the therapeutic efficacy of anti-GD2-based NIR-PIT using anti-GD2 mAb conjugated to the photoabsorber IR700 (anti-GD2-IR700) in human NB cells. Methods: We used 3 human NB cell lines, including IMR-32, CHP-134 and SK-N-SH. The expression of GD2 on the cell surface of NB cells was analyzed by flow cytometric analysis. Anti-GD2-IR700 was synthesized by incubating anti-GD2 mAb and IR700. The mixture was purified with a Sephadex G50 column. The antitumor effect of anti-GD2-IR700 was evaluated using XTT assay. NB cells were incubated with anti-GD2-IR700, anti-GD2 mAb or PBS and NIR light was irradiated at 2.0J/cm2. Results: IMR-32 and CHP-134 cells, but not SK-N-SH cells, expressed GD2 protein on the cell surface. In GD2-positive IMR-32 and CHP-134 cells, administration of anti-GD2-IR700 significantly suppressed the cell viability compared to anti-GD2 mAb or PBS when combined with NIR light irradiation. In contrast, in GD2-negative SK-N-SH cells, anti-GD2-IR700 showed no significant inhibition of cell viability in combination with NIR light irradiation. Conclusion: These results suggest that NIR-PIT using an anti-GD2-IR700 is a promising antitumor strategy to promote the therapeutic efficacy of anti-GD2 immunotherapy for high-risk NB. Citation Format: Hiroshi Nouso, Hiroshi Tazawa, Terutaka Tanimoto, Morimichi Tani, Takanori Oyama, Hiroaki Sato, Kazuhiro Noma, Shunsuke Kagawa, Hisataka Kobayashi, Takuo Noda, Toshiyoshi Fujiwara. Development of near-infrared photoimmunotherapy targeting GD2-positive neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3831.
Body Surface Potential Distributions During Idiopathic Ventricular Tachycardia
Authors: DidierKlug, AngeFerracci, FranckMolin, MarcDubuc, PierreSavard, TeresaKus, FrançoisHélie, RenéCardinal, RéginaldNadeau
Journal: Circulation (1995)

Background The purpose of this report is to describe the body surface potential maps (BSPMs) during idiopathic ventricular tachycardia (VT) and to determine what differences exist between different idiopathic VT morphologies. Methods and Results We performed BSPMs during VT on 12 consecutive patients (3 women and 9 men; mean age, 42±13 years) presenting symptomatic idiopathic VT referred to our institution for electrophysiological study. Basal ECG, chest radiograph, and echocardiogram were normal in all patients. Clinical tachycardia showed left bundle branch block pattern (LBBB) in 9 patients, with sustained VT in 5 and nonsustained VT in 4, and right bundle branch block pattern (RBBB) in 3 with sustained VT. We found a unique pattern of BSPMs in each of the 9 patients during idiopathic LBBB VT configuration, whether sustained or nonsustained VT. This pattern appeared at the onset of the QRS and remained stable during the whole QRS complex. The area of minimal potential located in the upper anterior part...
Delayed Surgery of Traumatic Aortic Rupture
Authors: RossellaFattori, FrancescaCelletti, PaolaBertaccini, RobertoGalli, DavidePacini, AngeloPierangeli, GiampaoloGavelli
Journal: Circulation (1996)

Background Traumatic aortic rupture (TAR) is a pathological entity with a high mortality, both spontaneous and perioperative. Delayed surgical repair has been proposed when associated lesions are stabilized. The aim of this study was to validate MRI for detecting both the presence and type of TAR and to monitor posttraumatic aneurysm and associated lesions. Methods and Results Twenty-four consecutive patients with acute chest trauma and suspected aortic rupture, as suggested by emergency CT or chest radiographs, were subjected to MRI and/or angiography in random order. Such parameters as the presence and type of lesion; presence of periaortic, pericardial, mediastinal, or pleural effusion; and presence of associated lesions were considered in every patient. Follow-up imaging was performed exclusively by MRI every 1 to 2 months. TAR was present in 20 patients. No patient underwent surgery in the acute phase; 14 patients underwent surgery at 6.8±2.7 months; 5 are waiting for surgery; and 1 healed spontaneou...
Remodeling of In-Stent Neointima, Which Became Thinner and Transparent Over 3 Years
Authors: MasanoriAsakura, YasunoriUeda, ShinsukeNanto, AtsushiHirayama, TakayoshiAdachi, MasafumiKitakaze, MasatsuguHori, KazuhisaKodama
Journal: Circulation (1998)

Background—Recently, it has been reported that the luminal diameter shows phasic changes after stenting: the progression of luminal narrowing followed by its regression. To elucidate the mechanisms involved in the phasic changes in luminal diameter after stenting, we examined the changes in neointimal thickness and the appearance of neointima by a series of angiographic and angioscopic observations for 3 years after stent implantation. Methods and Results—In 12 patients who received a Wiktor coronary stent, serial angiographic and angioscopic examinations were performed immediately, 2 to 4 weeks, 3 months, 6 months, and 3 years after the stenting without repetition of angioplasty. Neointimal thickness was determined by angiography as the difference between stent and luminal diameters. The angioscopic appearance of neointima over the stent was classified as transparent or nontransparent according to the visibility of the majority of the stent. Neointimal thickness increased significantly at 3 months (0.75±...
Abstract 2659: <i>GLUT1</i> variants and the prognosis of patients with NSCLC after surgery
Authors: Shin Yup Lee, Sook Kyung Do, Jin Eun Choi, Michael Neugent, Justin Goodwin, Jung-whan Kim, Jae Yong Park
Journal: Cancer Research (2018)

Abstract Background This study was conducted to investigate whether polymorphisms of glucose transporter 1 (GLUT1) gene are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Methods Five single nucleotide polymorphisms (SNPs) in GLUT1 were investigated in a total of 354 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) was analyzed. Results Among the five SNPs investigated, two SNPs (GLUT1 rs3820589T&amp;gt;A and rs4658G&amp;gt;C) were significantly associated with OS in multivariate analyses. GLUT1 rs3820589T&amp;gt;A was associated with significantly better OS (adjusted hazard ratio [aHR] = 0.57, 95% confidence interval [CI] = 0.34-0.94, P = 0.03, under dominant model), and rs4658G&amp;gt;C was associated with significantly worse OS (aHR = 1.91, 95% CI = 1.09-3.33, P = 0.02, under recessive model). In the stratified analysis by tumor histology, the effect of these SNPs on OS was only significant in squamous cell carcinoma, but not in adenocarcinoma. When the two SNPs were combined, OS decreased as the number of bad genotypes increased (Ptrend = 4 × 10-3). Conclusion This study suggests that genetic variation in GLUT1 may be useful in predicting survival of patients with early stage NSCLC. Citation Format: Shin Yup Lee, Sook Kyung Do, Jin Eun Choi, Michael Neugent, Justin Goodwin, Jung-whan Kim, Jae Yong Park. GLUT1 variants and the prognosis of patients with NSCLC after surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2659.
Abstract 4516: A new MLH1 rabbit monoclonal antibody for immunohistochemical application
Authors: Sean Cobb, Hongyang Pan, Qiong Yang, Jackie Chan, Julia Wu, Jason Law, Aihua Li
Journal: Cancer Research (2018)

Abstract Background: MLH1, a DNA mismatch repair gene, plays a critical role in colorectal cancer (CRC) development. Loss of nuclear MLH1 is attributed to hypermethylation of its promoter, occurring in 78% of microsatellite instability (MSI) which composes 15% of all CRC. Immunohistochemical (IHC) analysis of MLH1 in CRC is routinely performed in pathology laboratories, but remains challenging with the current selection of available MLH1 antibodies. Here we report a new MLH1 rabbit monoclonal antibody (RabMAb) developed with RabMAb® technology, designated as clone EP481. Design: Sera collected from rabbits immunized with recombinant MLH1 protein were screened by ELISA, WB, and IHC. After fusion, antibody from a final hybridoma cell line was further characterized by extensive IHC testing using formalin-fixed paraffin-embedded human normal and tumor tissue microarrays (TMAs) comprised of 99 CRCs. EP481 performance was compared against MLH1 mouse monoclonal antibodies, G168-15, G168-728, and the current benchmark, ES05. Cases without tumor cell staining were considered negative; those also lacking stroma staining were excluded, as it could not be determined if there was germline mutation or poor tissue quality. Agreement was evaluated with Cohen's kappa. Results: An 85 kDa MLH1 protein was detected by WB in SW480 cell lysate, but absent in the MLH1-negative cell line, HCT116. IHC analysis of EP481 was positive in normal epithelium and surrounding stroma, but negative in 10% of tumors. G168-728 showed nonspecific cytoplasmic staining and deviated from its counterparts. Concordance data (Table 1) demonstrates that EP481 is equivalent with ES05 and incongruous with G168-15. Conclusion: The RabMAb MLH1 antibody, clone EP481, specifically labels normal cells and is absent in 10% of CRCs. This finding is consistent with both literature and the gold-standard anti-mouse clone, ES05. EP481 is a new alternative for MLH1 IHC and a promising tool to identify MSI in CRC. Table 1. Concordance staining of MLH1 clone EP481 with clones ES05 and 168-15 on CRC TMA.ES05 +ES05 -Total168-15 +168-15 -TotalEP481 +7417566975EP481 -178268Total75883681583Cohen's kappaRatersCoefficientAgreementEP481/ES0586%ExcellentEP481/168-1545%Moderate Citation Format: Sean Cobb, Hongyang Pan, Qiong Yang, Jackie Chan, Julia Wu, Jason Law, Aihua Li. A new MLH1 rabbit monoclonal antibody for immunohistochemical application [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4516.
Potassium Exchange in the Dog Heart in Situ
Authors: Guntergrupp, CharlesAstrida
Journal: Circulation Research (1963)

Coronary perfusion with constant flow and constant specific activity permitted an estimate of the transmembrane fluxes of potassium in both directions in the dog heart in situ. The determination of efflux was based on the washout characteristics. Perfusion pressure and coronary flow within the limits studied have little influence on efflux. The estimate of influx involved correction of experimental data using the efflux from the same experiment and is therefore less accurate; it is subject to changes due to alterations in collateral blood supply of the perfusion area. The efflux varies by 50% from heart to heart, averaging 0.68 mEq K+/kg and min at an average heart rate of 130 beats/min. Changes in heart rate reveal that 1.65 µEq K+/kg are exchanged per beat above the resting flux of the nonbeating heart; the latter was estimated by extrapolation to be 0.55 mEq K+/kg and min.
Abstract P036: Exploring Systems Thinking as an Underlying Mechanism in Improving Healthy Lifestyles of Overweight and Obese Adolescents: Psychometrics of the Systems Thinking Scale for Adolescent Behavior Change
Authors: Shirley M Moore
Journal: Circulation (2016)

We have learned from the past that interventions targeting health behavior change involve assisting participants to identify and make changes in the habitual systems in their daily routines. Although the skills to change these habitual systems involve systems thinking (the ability to recognize patterns, interactions and interdependencies in a set of activities), no current measure exists to assess the extent to which systems thinking influences health behavior change. Our team is currently investigating the mediating role of systems thinking in enhancing healthy eating and exercise in overweight and obese adolescents. The purpose of this study was to develop and conduct psychometric testing of the Systems Thinking Scale for Adolescent Behavior Change (STS-AB). In a first phase of this study, a panel of experts in systems thinking was used to develop an initial item set that was tested for understandability, content validity and stability in a small sample (N= 24) of adolescents enrolled in a weight management program. In a second phase, using a larger study of 359 urban adolescents enrolled in a weight management trail aged 10-13 (58% girls; 80% African American), factor analysis, reliability, and validity of the 16-item STS-AB were assessed. Results of an exploratory factor analysis of the STS-AB indicated a 1-factor solution with good factor loadings, ranging from .40 to .67. The internal consistency reliability coefficient was .87. Test-retest reliability of the STS-AB was .48, p&lt;.05. Systems thinking scores were higher in children who received systems thinking training compared to children not receiving training. Evidence of construct validity was supported by significant correlations with established measures of other variables commonly associated with health behavior change (motivation and self-efficacy for diet and physical activity). These findings indicate that the STS-AB is a valid and reliable measure of systems thinking for health behavior change in adolescents that can assist investigators to examine the extent to which systems thinking is a mechanism in health behavior change.
Abstract 11525: Blood Pressure Reduction and Increase of Circulating MicroRNA-126 Indicate Improvement of Vascular Endothelial Damage After Smoking Cessation Intervention in Middle-Aged Habitual Smokers
Authors: TomonoriSugiura, YasuakiDohi, SumiyoYamashita, AkimasaSanagawa, SoichiroIwaki, NobuyukiOhte, SatoshiFujii
Journal: Circulation (2014)

Introduction: Cigarette smoking promotes vascular endothelial damage and accelerates progression of atherosclerosis. The purpose of this study was (1) to examine effects of smoking cessation intervention on vascular function and (2) to investigate whether circulating level of microRNA-126 (miR-126), a vascular endothelium-enriched microRNA, would recover from smoking-related endothelial damage in middle-aged habitual smokers. Methods: Middle-aged male smokers (n=30) were enrolled and instructed to stop smoking. Their clinical profiles of vascular function and laboratory findings including serum levels of cotinine, a principal metabolite of nicotine, and expression of miR-126 were investigated at baseline and 8 weeks after the instruction. Vascular function for peripheral small vessels was assessed using End-PAT 2000 and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. The expression of miR-126 in plasma was analyzed by quantitative real-time PCR. Results: At baseline, serum co...