tbuckley/cabot-search huggingface dataset:
Abstract 2131: Paracrine cytokine pathways mediate metastasis of breast cancer to lymphatics
Authors: Kyungmin Ji, Zhiguo Zhao, Kamiar Moin, Yong Xu, Robert J. Gillies, Raymond R. Mattingly, Bonnie F. Sloane
Journal: Cancer Research (2018)

Abstract Lymphatics, rather than blood vessels, are the primary route for breast cancer metastasis. The presence of breast cancer cells in regional lymphatics, i.e., lymphatic metastasis, is an important prognostic factor for patients. Delineating molecular mechanisms by which the breast cancer cells migrate toward and infiltrate into lymphatics is crucial to designing new therapies to prevent metastatic dissemination. To study tumor:lymphatic interactions, we are using a three-dimensional (3D) heterotypic co-culture model of human breast cancer cells (hBCCs) grown with human microvascular lymphatic endothelial cells (hLECs) in novel chambers that we designed and fabricated. These chambers support growth of the 3D co-cultures, live-cell confocal imaging in real time and noninvasive collection of conditioned media for secretomic analyses. We use live-cell assays developed in our laboratory for quantitative analysis of temporal and dynamic changes in BCC:LEC interactions in correspondence with changes in their malignant and proteolytic phenotypes. We cultured hLECs in the presence and absence of human MDA-MB-231 (231) triple-negative BCCs in 3D cultures for 4 days. In mono-cultures, the 231 cells grow in clusters that exhibit a stellate morphology and hLECs form branching networks with central nodes. We observed that the volumes of 3D structures formed by LECs and 231 cells were significantly greater in co-cultures than in mono-cultures of either cell type. In addition, 231 cells infiltrate into the LEC networks with the infiltration increasing over the 4-day period as assessed by the degree of overlap between 231 cells and hLECs in 3D reconstructions of the co-cultures. Moreover, soluble factors from LECs increase invasive outgrowths of 231 structures. This was demonstrated in 231 cells grown in media conditioned by LECs and in parallel co-cultures of 231 cells and LECs. The induction of invasiveness by LEC conditioned media is reduced by boiling and repeated freeze/thawing, suggesting that the active factor(s) is a protein. Our preliminary results suggest that LECs secrete soluble factors that may be therapeutic targets for reducing invasion of BCCs into lymphatic networks. Citation Format: Kyungmin Ji, Zhiguo Zhao, Kamiar Moin, Yong Xu, Robert J. Gillies, Raymond R. Mattingly, Bonnie F. Sloane. Paracrine cytokine pathways mediate metastasis of breast cancer to lymphatics [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 2131.
Abstract 19228: Patient Perceptions on Improving Follow-Up After Heart Failure Hospitalization
Authors: Rachel D’Amico, Timothy Adesanya, Stefanie Hatfield, Shannon Willis, Rodney Sturdivant, Randi E Foraker, Philip Binkley, William T Abraham, Khadijah Breathett
Journal: Circulation (2016)

Background: Follow-up after heart failure hospitalization (HFH) is below target especially in lower socioeconomic groups. The patient-centered solutions for improving follow-up post HFH have not been well studied. Methods: Face-to-face surveys were conducted with 83 adult patients admitted for HFH to Ohio State University Hospital East, centered in a low-income area of Columbus, Ohio, from 2/2015-2/2016. Patient perceptions of methods to improve follow-up post HFH and likelihood of using interventions were investigated using Likert scale: 1=very much to 5=not at all. Results were analyzed by Wilcoxon signed rank test with Bonferroni adjustment. Results: The response rate was 70%. The annual household income was <$35,000 for 49% of patients. An appointment near the patient’s home was the most desired intervention (77% ranking the highest), followed by reminder message (73%), transportation to appointment (63%), and elimination of co-payment (59%) (Figure). Rankings were not significantly different with Bon...
Non-surgical Retrieval of a Broken Segment of Steel Spring Guide from the Right Atrium and Inferior Vena Cava
Authors: Johnthomas, Brucesinclair-Smith, Dennisbloomfield, Asghardavachi
Journal: Circulation (1964)

The recovery of a broken segment of a steel spring guide from the right atrium and inferior vena cava without surgical intervention has been reported. The ready accessibility of an adequate instrument for retrieval of such intravascular bodies is recommended. It is possible that such an instrument may be also designed for myocardial biopsy. The relative ease of breakage probably points to a defect in the guides and a re-evaluation of the design and manufacture seems to be indicated.
Abstract 1645: Innovative discovery of therapeutic plateletpheresis in patients with thrombocytosis using the Fresenius COM.TEC
Authors: Yanxia Jin, Guolin Yuan, Fuling Zhou
Journal: Cancer Research (2018)

Abstract Plateletpheresis is an important therapeutic method for treatment of patients with myeloproliferative neoplasms (MPN) presenting with thrombocytosis. This study analysed the collection efficiency of plateletpheresis (CEPP) for 94 patients with thrombocytosis who underwent plateletpheresis by Fresenius COM.TEC machine, especially analysed the CEPP for enrolled patients with PLT count at 500-1000 × 109/l. The results indicated that this device could significantly decreased PLT count, and with mean CEPP of 24.23±17.42% that ranges from 3.18% to 78.46%. Further analysis shows that the PLT counts were 500-800 × 109/l for patients, which CEPP was above 42.1% with a lower pooled WBC and RBC. Paired t-test suggested that the red blood cell (RBC) counts, PLT counts, white blood cell (WBC) counts, monocyte counts and haematocrit (HCT) significantly decreased after plateletpheresis. Bivariate correlation and multiple logistic regression analysis showed that PLT count groups, hemoglobin (HGB) before apheresis were greatly correlated with CEPP. We suggest that the device is effective at reducing platelet counts with acceptable efficiency and it is available for plateletpheresis when the PLT counts about 500-800 × 109/l for patients with higher HGB pre-apheresis in female patients. Citation Format: Yanxia Jin, Guolin Yuan, Fuling Zhou. Innovative discovery of therapeutic plateletpheresis in patients with thrombocytosis using the Fresenius COM.TEC [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 1645.
Cell DistensionInduced Increase of the Delayed Rectifier K+ Current in Guinea Pig Ventricular Myocytes
Authors: ZhurenWang, TamotsuMitsuiye, AkinoriNoma
Journal: Circulation Research (1996)

Abstract Single ventricular myocytes of guinea pig heart were distended by applying a positive pressure of 5 to 20 mm Hg in the pipette during the whole-cell voltage clamp. The amplitude of delayed rectifier K+ current (IK) was increased by ≈1.5 times, whereas the inward rectifier K+ current was scarcely affected. The increase of IK was reversible by applying a negative pressure of −10 to −30 mm Hg accompanied by shrinkage of the inflated cell. This response of IK was largely attributed to the E-4031–insensitive component of IK. The fully activated current amplitude, measured using long-lasting depolarizing pulses (>30 seconds) to +60 mV, was increased by the cell distension. The activation time course of IK during the long pulse consisted of more than three exponential components, and the slowest time constant was decreased by the distension from control 20.2±7.7 seconds (n=4) to 7.6±1.6 seconds (n=5). We failed to detect an involvement of microtubules or microfilaments, protein kinase C, and Ca2+ in the...
Abstract 3225: Cutaneous nevi and cancer risk among US women
Authors: Xin Li, Wenting Wu, Edward Giovannucci, Meir J. Stampfer, Xiang Gao, Jiali Han
Journal: Cancer Research (2018)

Abstract Background: Longer telomeres have been linked to elevated cutaneous nevus number. Recently, a large Mendelian randomization study identified a positive association between telomere length and risk of cancer. We hypothesized that higher nevus count, as a phenotypic marker of longer telomere length, may be associated with increased risk of cancer development. Methods: We prospectively examined the association between nevus count and total as well as site-specific cancer risk among participants in the Nurses' Health Study (NHS, 1986-2012) and the Nurses' Health Study 2 (NHS2, 1989-2013). Results: During 3,941,477 person-years of follow-up, we documented a total of 24,428 cancer cases (16,297 in the NHS and 8,131 in the NHS2). Compared to participants who had no nevi, the multivariate HRs were 1.08 (95%, 1.05-1.11) for women with 1-5 nevi, 1.15 (95%, 1.09-1.21) for those who had 6-14 nevi, and 1.26 (95%, 1.18-1.34) for those with 15 or more nevi (p trend &amp;lt; 0.0001). We did not observe significant interactions between the number of nevi and other covariates in the multivariable-adjusted model. We also conducted secondary analyses by excluding 1) only melanoma and 2) both melanoma and breast cancer from the outcomes of interest, respectively. The results were very similar to those of our primary analysis using all cancer sites. For individual cancer sites, most of the associations with mole counts were positive but not statistically significant. Conclusion: We identified the number of cutaneous nevi as a phenotypic marker associated with cancer risk, which may possibly be explained by telomere biology. Citation Format: Xin Li, Wenting Wu, Edward Giovannucci, Meir J. Stampfer, Xiang Gao, Jiali Han. Cutaneous nevi and cancer risk among US women [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 3225.
Abstract 3378: Variance in the distance between chromosome territories 9 and 22 in lymphocytes from peripheral blood healthy subjects: A proof of concept for a possible risk factor in chronic myeloid leukemia
Authors: David G. Vallejo, Eunice Fabian, Luis A. Herrera
Journal: Cancer Research (2018)

Abstract The objective of our study was to assess the variations in the 3D organization of Chromosome Territories (CT) of chromosomes 9 and 22 in lymphocytes from healthy subjects. The differences in the distances of CTs 9 and 22 between subjects may provide a new perspective in the predisposition for specific chromosome translocations. We quantified the intra- and inter-subject variation in the distance of CT 9 and 22 as a proof of concept for new questions on the physiological and pathological effects of these differences. Methods: Blood samples from healthy subjects were processed for the isolation of lymphocytes with Ficoll as the gradient media. After the isolation, we fixed the cells directly onto coverslips for a 3D Fish protocol with 9 and 22 whole chromosome probes. Our protocol has been standardized to maintain the integrity of the nucleus with only minor changes in its volume. After the hybridization, we used the Elyra System of Zeiss to obtain super resolution images in Z stack. The images were processed with the Imaris software for its 3D reconstruction, measurement (distances, volumes and colocalization) and analysis. Results: The CTs 9 and 22 behave differently in peripheral blood lymphocytes. The CT 22 has a more internal position (closer to the center of the nucleus) in comparison with the CT 9, which can be seen most of the times in contact with the border of the nucleus. The CT 22 occupies a smaller volume than CT 9, which has almost a twice as larger volume. The CTs 9 have a polarized distribution inside the nucleus, therefore the distance between the CT 9-9 was larger (~7.3 μm ± 0.9) than the distance between CT 22-22. Although the position of the CTs was highly variable in cells from the same individual, we found a statistically significant difference in the inter-individual distance between CT 9-9 and the minimal distance between CT 9-22. Conclusion: Our study suggests that there are differences in the distribution of CT in lymphocytes isolated from peripheral blood between our subjects. These differences could prove to be a new individual characteristic with important implications in the predisposition for specific diseases, mainly to those related with chromosomal rearrangements. Citation Format: David G. Vallejo, Eunice Fabian, Luis A. Herrera. Variance in the distance between chromosome territories 9 and 22 in lymphocytes from peripheral blood healthy subjects: A proof of concept for a possible risk factor in chronic myeloid leukemia [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 3378.
Abstract 18551: Predictors of Heart Failure and Death in a High Risk Diabetic Population: The DAVID-Berg Study
Authors: Mauro Gori, Paolo Canova, Alice Calabrese, Giovanni Cioffi, Attilio Iacovoni, Aurelia Grosu, Alessandra Fontana, Paola Ferrari, Renata De Maria, Filippo Taddei, Alessandro Filippi, Maria Rosaria Rutili, Luigi Donzelli, Marina Parolini, Antonello Gavazzi, Michele Senni
Journal: Circulation (2014)

Introduction: Diabetic subjects are at high risk of heart failure (HF) and death. Few data are available on the predictive value of NTproBNP, ECG, and echocardiogram in this population Hypothesis: A screening strategy with NTproBNP, ECG, and echo may improve prediction of HF/death events in a diabetic population in HF-stages A &amp; B, beyond clinical data Methods: In 2008, among 4047 subjects aged &gt;55 and &lt;80 yrs treated by three general medicine group practices, the DAVID-Berg study enrolled all subjects with diabetes &amp;/or hypertension &amp;/or cardiovascular disease, without history/symptoms/signs of HF (n=623). Subjects underwent clinical visit, 12-lead ECG, echocardiogram, NTproBNP point of care testing. Recently data on HF/death events have been prospectively collected for all diabetic subjects included in the study (n=198) Results: Median age of the study population was 69 yrs, 62% were men, mostly hypertensive (86%) with known cardiovascular disease (44%). During a median follow-up of 5.2 [4.9,5.5] yrs there were 45 HF/death. At Cox regression analyses univariate predictors of events were known cardiovascular disease, insulin therapy, chronic kidney dysfunction (CKD), NTproBNP≥300 pg/mL, abnormal ECG (atrial fibrillation &amp;/or LV hypertrophy &amp;/or bundle branch block &amp;/or Q wave), left atrial volume index (LAVI)≥40 mL/m 2 , LV ejection fraction (LVEF)≤55%, and LV mass index. At multivariate analyses (stepwise forward selection applied to univariate predictors), clinical variables (CKD and known cardiovascular disease), ECG (HR 2.66 [95% CI 1.08-6.55]), LAVI≥40 mL/m 2 (HR 2.50 [95% CI 1.28-4.89]), and LVEF≤55% (HR 2.70 [95% CI 1.45-5.04]) remained significantly associated with the outcome. Adding sequentially NTproBNP, ECG, and echo (LAVI, LVEF) to clinical data improved event prediction (Figure) Conclusions: High risk diabetic subjects may be correctly risk stratified integrating sequentially clinical data with NTproBNP, ECG, and echocardiogram
Abstract 3880: Peptide-targeted chemotherapy for pancreatic cancer
Authors: Chin-Tarng Lin, Chen-Der Wu, Jen-Chieh Lee, Han-Chung Wu, Chung-Wei Lee, Chin-Feng Lin, Ming-Chieh Hsu
Journal: Cancer Research (2018)

Abstract The purpose of this abstract was to assess the efficacy of peptide targeted chemotherapy for pancreatic carcinoma. Previously we have constructed four peptides that bind specifically to cancer cell lines, which were derived from three different carcinoma cell lines and their vascular endothelia: L-peptide: (L-P, anti-cancer cell membrane), RLLDTNRPLLPY; SP-94-P (anti-hepato-pancreatic cancer cell membrane), SFSHHTPILP; PC5-52-peptide (anti-tumor endothelia), SVSVGMKPSPRP; and control peptide, RLLDTNRGGGGG. These peptides were linked to pegylated liposomal iron oxide nanoparticles to identify the targeted tumor cells and vascular endothelia using MRI analysis, and were also linked to dextran coated liposomal doxorubicin (L-D) for treatment of non-obese diabetic, severe combined immunodeficiency (NOD-SCID) mice bearing pancreatic cancer cell (PANC-1) xenografts. Our results demonstrated that the tumor intensity of MRI is clearly decreased after SP-94-P-iron oxide was applied, and that in combination of application of L-P linked L-D (L-P-L-D) plus SP-94-P linked L-D (SP-94-P-L-D) and PC5-52-P linked L-D (PC5-52-P-L-D), they could inhibit pancreatic tumor growth with very mild adverse events. The use of the control peptide linked L-D also led to a decrease of the xenograft size, but also induced marked apoptotic change of their visceral organs. It is concluded that the combination of L-P-L-D, SP-94-P-L-D and PC5-52-P-L-D to treat pancreatic cancer xenograft in NOD SCID mice can clearly inhibit pancreatic cancer growth with minimal adverse events. Citation Format: Chin-Tarng Lin, Chen-Der Wu, Jen-Chieh Lee, Han-Chung Wu, Chung-Wei Lee, Chin-Feng Lin, Ming-Chieh Hsu. Peptide-targeted chemotherapy for pancreatic cancer [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 3880.
Abstract 4906: Effect of gender on the rodent pharmacokinetics of ON 123300, a dual inhibitor of ARK5 and CDK4/6, for the treatment of cancer
Authors: Chen Ren, Jennypher Mudunuru, David Taft, Manoj Maniar
Journal: Cancer Research (2018)

Abstract Purpose: To evaluate gender differences in the metabolism of ON 123300 in rats in vitro and in vivo. ON 123300, a novel small molecule dual inhibitor of the c-MYC activated kinases ARK5 and CDK4/6, is being developed by Onconova Therapeutics, Inc. as a novel anti-cancer drug candidate. Methods: In vitro metabolism experiments were performed in rat liver microsomes from male and female donors. ON 123300 was incubated with microsomes, and samples were withdrawn at specified times over 60 minutes and, immediately quenched and centrifuged. The supernatant was analyzed for ON 123300 and its metabolites by HPLC. An in vivo pharmacokinetic study was performed in male and female SD rats. ON 123300 was administered as a single oral dose (100 mg/kg), and blood samples were collected over 24 hours. ON 123300 concentrations were measured by LC-MS/MS. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results: The results are provided in Table 1. ON 123300 displayed more rapid microsomal degradation in vitro (increase of Clint) in males compared to females. This translated into a significantly higher exposure of ON 123300 (3 fold increase of AUC) following oral administration to female rats. Based on these results, the higher plasma concentrations observed in females can be primarily attributed to reduced hepatic clearance compared to males. Conclusions: Gender differences in pharmacokinetics and pharmacodynamics can potentially impact the design of safe and effective dosing regimens for treatments. This investigation demonstrated a significantly lower metabolism of ON 123300 in female rats, which resulted in dramatically high systemic exposure. Additional testing is warranted to assess the potential clinical implications of these findings. Table 1. ON 123300 In Vitro and In Vivo Pharmacokinetic Parameters In Vitro Metabolism (n = 2/group)In Vivo Pharmacokinetics (n = 5/group)Parameter (mean)MalesFemalesParameter (mean± SD)MalesFemalest1/2 (min)10.838.2Tmax (hr)2.3 ± 1.60.6 ± 0.2Clint (ml/min/mg)13036.7Cmax (ng/ml)321 ± 66.01253 ± 660Predicted In Vivo Cl(ml/min/kg)a239.267.5AUC0-∞ (ng-hr/ml)1803 ± 7575520 ± 2163Cl/F (ml/min/kg)1116 ± 474390 ± 269t1/2 (hr)1.9 ± 0.503.0 ± 0.5 apredicted from venous equilibration model assuming rat blood flow = 13.8 ml/min, 99% protein binding and blood:plasma ratio = 1 Citation Format: Chen Ren, Jennypher Mudunuru, David Taft, Manoj Maniar. Effect of gender on the rodent pharmacokinetics of ON 123300, a dual inhibitor of ARK5 and CDK4/6, for the treatment of cancer [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 4906.
Abstract 19663: Failed Delayed Sternal Closure Following Neonatal Cardiac Surgery Predicted by High Mean Airway Pressure and Associated with Increased Post-operative Mortality
Authors: Dashiell Massey, Kathryn A Williams, Ravi R Thiagarajan, Frank Pigula, Catherine K Allan
Journal: Circulation (2014)

Background: Myocardial edema, increased lung water, and anasarca are common following neonatal cardiac surgery with cardiopulmonary bypass and amplify the risk of hemodynamic instability and inadequate ventilation following sternal closure. Delayed sternal closure (DSC) in the intensive care unit one or more days following surgery is a common strategy to mitigate this risk, but has been associated with increased risk of infection. In addition, failed DSC has previously been identified as a risk factor for mortality. This study sought to identify predictor variables and determine impact of failed DSC. Methods: Records of all neonates undergoing DSC in the cardiac intensive care unit (CICU) following surgery with cardiopulmonary bypass between January 2008 and May 2013 were reviewed. Pre-operative, intra-operative and post-operative variables were compared for those patients who failed DSC versus those who did not. Continuous variables were compared utilizing Wilcoxon’s test and categorical variables using Fisher’s exact test. Results: Of 256 neonates undergoing DSC in the CICU, 22 failed first attempt at DSC. No significant difference between the two groups was appreciated in age, weight, or bypass (cross clamp, circulatory arrest, and total) times. Comparing DSC failures to successes, significantly more failures: followed Stage I palliation (63% vs. 31%); occurred later (post-operative day 4.7 vs. 2.8, p = 0.009); and were proceeded by higher mean airway pressures (9 vs. 8 cm H2O, p = 0.04), peak inspiratory pressure (27 vs. 24, p = 0.002), and inotrope score (12.1 vs. 9.6, p = 0.06). There was no association with systolic blood pressure or lactate prior to DSC. Failed DSC was associated with increased duration of mechanical ventilation (41.6 vs 7.4 days, p &lt; 0.001), length of ICU stay (44.3 vs 12.0 days, p &lt; 0.001), and mortality (38 vs 3%, p &lt; 0.001). Conclusions: Mortality for patients who fail the first ICU attempt at delayed sternal closure is significantly higher than for those with successful sternal closure. Ventilatory pressures but not hemodynamic variables prior to DSC differed significantly between the two groups. First attempt at DSC was later in those who failed, suggesting that clinicians had a priori identified these patients as higher risk.